Bioactive concentrates and uses thereof

ABSTRACT

The present invention relates to concentrates obtained from extraction from Cannabis, preferably cannabinoid and/or terpene concentrates, and formulation of the concentrates, particularly for use for direct vaporization, infusion into edible matrices, in electronic inhalation devices, and as nutraceuticals.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/781,491 filed Mar. 14, 2013 and to U.S. Provisional PatentApplication No. 61/781,479 filed Mar. 14, 2013, the contents of each ofwhich are incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to concentrates obtained from extractionfrom Cannabis, preferably cannabinoid and/or terpene concentrates, andformulation of the concentrates, particularly for use for directvaporization, infusion into edible matrices, in electronic inhalationdevices, and as nutraceuticals.

BACKGROUND OF THE INVENTION

Cannabinoids are a class of diverse chemical compounds that activatecannabinoid receptors. These include the endocannabinoids (producednaturally in the body by humans and animals), the phytocannabinoids(found in Cannabis and some other plants), and synthetic cannabinoids(produced chemically by humans). The most notable cannabinoid is thephytocannabinoid Δ9-tetrahydrocannabinol (THC), the primary psychoactivecompound of Cannabis.

As mentioned, the main cannabinoid is Δ⁹-tetrahydrocannabinol (THC),which is recognized as the major psychoactive euphoriant responsible forthe characteristic intoxication (‘high’) which follows the smoking oringestion of Cannabis. High THC doses produce hallucinogenic effects. Inaddition to THC, several less potent metabolites and related compounds,such as the also psychoactive Δ 8-THC and cannabinol (CBN) are found inthe Cannabis plant. Another major compound is cannabidiol (CBD), whichhas antagonistic effects to THC because it is a sedative compound. Theratio of THC to CBD in the plant is significant in terms ofpsychoactivity and is genetically determined.

A number of chemotypes exist within Cannabis. These are plants which arevisually and botanically identical but which are chemically dissimilar.One type referred to as the fiber- or hemp-type contains predominantlyCBD and only trace amounts of THC. Conversely, drug-type plants producepredominantly THC with trace quantities of CBD.

The issue is further complicated by the existence of an intermediateplant which contains approximately equal amounts of both THC and CBD.The concentrations of these and other cannabinoids vary enormously inpractice depending on plant breeding and cultivation techniques and onpost-harvest handling. THC is a highly unstable compound, breaking downin air and light to a number of inactive molecules, one of which,cannabinol (CBN), is commonly found in Cannabis products as they age.Other relatively abundant, and in certain rare chemotypes, predominantcannabinoids include cannabigerol (CBG), cannabichromene (CBC),tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV) but in generallittle is known about the biological activities of these and theremaining less frequently occurring molecules.

Most pharmacological research has focused on THC and CBD. However, whileTHC is responsible for many of the effects of Cannabis drugs, it isimportant to bear in mind that THC and Cannabis are not synonymous for anumber of reasons. Firstly, THC does not exist as such in the plantmaterial but rather it is found as a carboxylic acid (THCA), as areother cannabinoids. While less studied, these carboxylic acidderivatives show pharmacological potential as well. These acids (THCAand CBDA) decompose slowly during storage to the correspondingchemically neutral but pharmacologically potent THC and CBD. Thisconversion is speeded up by the high temperatures involved in smokingand to a lesser extent by cooking or baking the drugs. Secondly, theTHC/CBD ratio can markedly alter the effects of the drugs. Thirdly, someof the non-cannabinoid compounds from the plant may modulate thepharmacological effects of the cannabinoids. Terpenoids, which areresponsible for the characteristic smell and flavor of Cannabis, havebeen postulated as influencing the effects yet experimental evidence isscarce. Some 1% by weight of the plant is composed of a mixture of 20flavonoid compounds which are well known as antioxidants and which alsoscavenge damaging free radicals.

There has been considerable research regarding the first cannabinoiddiscovered in the Cannabis plant, cannabinol (CBN). While generallyconsidered an unwanted degradation product of Δ9 Tetrahydrocannabinol(THC), CBN is a weak agonist of the CB1 and CB2 receptors. CBN isbelieved to cause drowsiness alone or when combined with CBD, THC,Cannagiberol (CBG), THCV, or Cannabichromene (CBC). As an isolatedcompound, CBN has shown moderate toxicity in animal models. Combinedwith other cannabinoids, THC, CBD, CBG, or CBC, it is believed that thetoxicity is reduced due to the mediating effects of the othercannabinoids.

As can be seen, most research around active components of Cannabis hascentered on THC and CBD. To this extract, there are many descriptions ofprocesses making THC extracts and of products incorporating theextracts. However, there are relatively few reports of methods forextracting other bioactive compounds from Cannabis and the use of suchbioactive extracts in a nutraceutical context. Accordingly, what isneeded in the art are methods for producing and formulating bioactiveextracts from Cannabis that contain desired compounds in addition to orother than THC.

SUMMARY OF THE INVENTION

The present invention relates to concentrates obtained from extractionfrom Cannabis, preferably cannabinoid and/or terpene concentrates, andformulation of the concentrates, particularly for use for directvaporization, infusion into edible matrices, in electronic inhalationdevices, and as nutraceuticals.

In some embodiments, the present invention provides processes forpreparing cannabinoid and/or terpenoid extracts for human consumptioncomprising: (a) concentrating glandular trichomes from Cannabis plantmaterial; (b) passing a solvent though the plant material to produce acannabinoid/terpenoid-containing eluate; (c) filtering solids from theeluate; (d) refining the eluate to remove undesirable impurities; and(e) processing the eluate into a consumable form. In some embodiments,the refining comprises: (i) distilling the eluate; (ii) resuspendingeluate in polar solvent; and (iii) cooling resuspended eluate toprecipitate out undesirable impurities. In some embodiments, therefining comprises: (i) adding eluate to non-polar solvent; (ii) addingconcentrated brine solution; (iii) agitating vigorously; (iv) drainingoff brine solution; and (v) treating the eluate with desiccant. In someembodiments, the methods further comprise the step of fractionating theeluate into fractions enriched for one or more cannabinoids and/orterpenoids. In some embodiments, the fractionating comprises passing theeluate over a column in the presence of solvents of progressivelydifferent polarities, and collecting fractions as they exit the column.In some embodiments, the fractionating comprises: (i) concentrating theeluate in a non-polar solvent; (ii) cooling the eluate solution to 20 to−200 C; and (iii) filtering crystals according to composition. In someembodiments, the refining comprises exposing eluate to UV light for atleast 30 minutes to degrade chlorophyll. In some embodiments, therefining comprises: (i) adding solvent and activated charcoal to eluate;(ii) mixing; (iii) filtering out activated charcoal; and (iv) removingsolvent. In some embodiments, processing the eluate into a consumableform comprises spray drying the eluate to produce a crystalline extract.In some embodiments, processing the eluate into a consumable formcomprises thin film evaporation. In some embodiments, processing theeluate into a consumable form comprises continuously stirring the eluatewith a whisk or auger until eluate is dried into a wax.

In some embodiments, the present invention provides a concentrateproduced by the foregoing methods.

In some embodiments, the present invention provides a concentratecomprising at least 1% w/w of at least one cannabinoid compound selectedfrom the group consisting of Cannabigerol (E)-CBG-C5, Cannabigerolmonomethyl ether (E)-CBGM-C5 A, Cannabigerolic acid A (Z)-CBGA-C5 A,Cannabigerovarin (E)-CBGV-C3, Cannabigerolic acid A (E)-CBGA-C5 A,Cannabigerolic acid A monomethyl ether (E)-CBGAM-C5 A andCannabigerovarinic acid A (E)-CBGVA-C3 A); (±)-Cannabichromene CBC-C5,(±)-Cannabichromenic acid A CBCA-C5 A, (±)-Cannabivarichromene,(±)-Cannabichromevarin CBCV-C3, (±)-Cannabichromevarinic acid A CBCVA-C3A); (−)-Cannabidiol CBD-C5, Cannabidiol momomethyl ether CBDM-C5,Cannabidiol-C4 CBD-C4, (−)-Cannabidivarin CBDV-C3, CannabidiorcolCBD-C1, Cannabidiolic acid CBDA-C5, Cannabidivarinic acid CBDVA-C3);Cannabinodiol CBND-C5, Cannabinodivarin CBND-C3);Δ9-Tetrahydrocannabinol Δ9-THC-C5, Δ9-Tetrahydrocannabinol-C4 Δ9-THC-C4,Δ9-Tetrahydrocannabivarin Δ9-THCV-C3, Δ9-Tetrahydrocannabiorcol,Δ9-THCO-C1, Δ9-Tetrahydrocannabinolic acid A Δ9-THCA-C5 A,Δ9-Tetrahydrocannabinolic acid B, Δ9-THCA-C5 B,Δ9-Tetrahydrocannabinolic acid-C4 A and/or B Δ9-THCA-C4 A and/or B,Δ9-Tetrahydro-cannabivarinic acid A Δ9-THCVA-C3 A,Δ9-Tetrahydrocannabiorcolic acid A and/or B Δ9-THCOA-C1 A and/or B),(−)-Δ8-trans-(6aR,10aR)-Δ8-Tetrahydrocannabinol Δ8-THC-C5,(−)-Δ8-trans-(6aR,10aR)-Tetrahydrocannabinolic acid A Δ8-THCA-C5 A,(−)-(6aS,10aR)-Δ9-Tetrahydrocannabinol (−)-cis-Δ9-THC-C5); CannabinolCBN-C5, Cannabinol-C4 CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2,Cannabiorcol CBN-C1, Cannabinolic acid A CBNA-C5 A, Cannabinol methylether CBNM-C5, (−)-(9R,10R)-trans-Cannabitriol (−)-trans-CBT-C5,(+)-(9S,10S)-Cannabitriol (+)-trans-CBT-C5, (±)-(9R,10S/9S,10R)—);Cannabitriol (±)-cis-CBT-C5, (−)-(9R,10R)-trans-10-O-Ethyl-cannabitriol(−)-trans-CBT-OEt-C5,(±)-(9R,10R/9S,10S)-Cannabitriol-C3(±)-trans-CBT-C3,8,9-Dihydroxy-Δ6a(10a)-tetrahydrocannabinol 8,9-Di-OH-CBT-C5,Cannabidiolic acid A cannabitriol ester CBDA-C5 9-OH-CBT-C5 ester,(−)-(6aR,9S,10S,10aR)-9,10-Dihydroxy-hexahydrocannabinol, Cannabiripsol,Cannabiripsol-C5, (−)-6a,7,10a-Trihydroxy-Δ9-tetrahydrocannabinol(−)-Cannabitetrol, 10-Oxo-Δ6a(10a)tetrahydrocannabinol OTHC);(5aS,6S,9R,9aR)-Cannabielsoin CBE-C5, (5aS,6S,9R,9aR)—C3-CannabielsoinCBE-C3, (5aS,6S,9R,9aR)-Cannabielsoic acid A CBEA-C5 A,(5aS,6S,9R,9aR)-Cannabielsoic acid B CBEA-C5 B;(5aS,6S,9R,9aR)—C3-Cannabielsoic acid B CBEA-C3 B, Cannabiglendol-C3OH-iso-HHCV-C3, Dehydrocannabifuran DCBF-C5, Cannabifuran CBF-C5),(−)-Δ7-trans-(1R,3R,6R)-Isotetrahydrocannabinol,(±)-Δ7-1,2-cis-(1R,3R,6S/1S,3 S,6R)-Isotetrahydrocannabivarin,(−)-Δ7-trans-(1R,3R,6R)-Isotetrahydrocannabivarin);(±)-(1aS,3aR,8bR,8cR)-Cannabicyclol CBL-C5,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclolic acid A CBLA-C5 A,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclovarin CBLV-C3; Cannabicitran CBT-C5);Cannabichromanone CBCN-C5, Cannabichromanone-C3 CBCN-C3, andCannabicoumaronone CBCON-C5); and at least 0.1% w/w of at least oneterpenoid selected from the group consisting of Alloaromadendrene, allylhexanoate, benzaldehyde, (Z)-α-cis-bergamotene, (Z)-α-trans-bergamotene,β-bisabolol, epi-α-bisabolol, β-bisabolene, borneol (camphol),cis-γ-bisabolene, borneol acetate (bornyl acetate), α-cadinene,camphene, camphor, cis-carveol, caryophyllene (β-caryophyllene),α-humulene (α-caryophyllene), γ-cadinene, Δ-3-carene, caryophylleneoxide, 1,8-cineole, citral A, citral B, cinnameldehyde, α-copaene(aglaiene), γ-curcumene, β-cymene, β-elemene, γ-elemene, ethyldecdienoate, ethyl maltol, ethyl propionate, ethylvanillin, eucalyptol,α-eudesmol, β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene((Z)-β-farnesene), trans-α-farnesene, trans-β-farnesene, trans-γbisabolene, fenchone, fenchol (norbornanol, β-fenchol), geraniol,α-guaiene, guaiol, methyl anthranilate, methyl salicylate,2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol,isoamyl acetate, lemenol, limonene, d-limonene (limonene), linolool(linalyl alcohol, β-linolool), α-longipinene, menthol, γ-muurolene,myrcene (β-myrcene), nerolidol, trans-nerolidol, nerol, β-ocimene(cis-ocimene), octyl acetate, α-phellandrene, phytol, α-pinene(2-pinene), β-pinene, pulegone, sabinene, cis-sabinene hydrate(cis-thujanol), β-selinene, α-selinene, γ-terpinene, terpinolene(isoterpine), terpineol (a terpineol), terpineol-4-ol, α-terpinene(terpilene), α-thujene (origanene), vanillin, viridiflorene (ledene),and α-ylange.

In some embodiments, the concentrate comprises at least 1%, 2%, 5%, or10% w/w of two or more of the cannabinoid compounds. In someembodiments, the concentrate comprises at least 1%, 2%, 5%, or 10% w/wof three or more of the cannabinoid compounds. In some embodiments, theconcentrate comprises at least 1%, 2%, 5%, or 10% w/w of four or more ofthe cannabinoid compounds. In some embodiments, the concentratecomprises at least 1%, 2%, 5%, or 10% w/w of five of the cannabinoidcompounds. In some embodiments, the concentrate comprises at least0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% w/w of two or more ofthe terpenoids. In some embodiments, the concentrate comprises at least0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% w/w of three or more ofthe terpenoids. In some embodiments, the concentrate comprises at least0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% of four of theterpenoids. In some embodiments, the concentrate comprises at least0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% w/w of five or more ofthe terpenoids. In some embodiments, the concentrate comprises at least0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or 5% w/w of ten or more ofthe terpenoids. In some embodiments, the concentrate is substantiallyfree of THC-type compounds. In some embodiments, the concentrate issubstantially free of CBN-type compounds.

In some embodiments, the concentrate comprise a total cannabinoidfraction of from about 45% to 98% w/w (calculated as a weight percentageof the total weight of the concentrate), most preferably about 65% to95% w/w total cannabinoid compounds (e.g., as listed above) and a totalterpenoid fraction of from about 0.1% to 5% w/w total terpenoids (e.g.,as listed above; calculated as a weight percentage of the total weightof the concentrate). In some embodiments, the total cannabinoid fractioncontains from about 62% to about 92% w/w or from about 75% to 92% w/wTCHA and THC combined (calculated as a weight percentage of the totalweight of the concentrate). In other embodiments, the total cannabinoidfraction comprises from about 40% to 95% w/w or from about 60% to 92%w/w of a combination of CBG, CBC and THCV (calculated as a weightpercentage of the total weight of the concentrate). As described above,the total cannabinoid fraction may additionally comprise at least 1%,2%, 5%, or 10% w/w of three or more of the cannabinoid compounds(calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the concentrate comprises at least1%, 2%, 5%, or 10% w/w of four or more of the cannabinoid compounds(calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the concentrate comprises at least1%, 2%, 5%, or 10% w/w of five or more of the cannabinoid compounds.Likewise, the total terpenoid fraction may additionally comprise atleast 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of two or more of theterpenoids (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w ofthree or more of the terpenoids (calculated as a weight percentage ofthe total weight of the concentrate). In some embodiments, the totalterpenoid fraction may additionally comprise at least 0.01%, 0.05%,0.1%, 0.2%, or 0.5% w/w of four or more of the terpenoids (calculated asa weight percentage of the total weight of the concentrate). In someembodiments, the total terpenoid fraction may additionally comprise atleast 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of five or more of theterpenoids (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w often or more of the terpenoids (calculated as a weight percentage of thetotal weight of the concentrate). It should be noted that in definingthe concentrates in weight percentage terms, the weight percentage ofthe combined components will not exceed 100%.

In some embodiments, the present invention provides an oral deliveryvehicle comprising a concentrate as described above.

In some embodiments, the present invention provides a chewing gumcomprising a concentrate as described above.

In some embodiments, the present invention provides a dietary supplementas described above.

In some embodiments, the present invention provides a food productcomprising a concentrate as described above.

In some embodiments, the present invention provides a thin film deliveryvehicle comprising a concentrate as described above.

In some embodiments, the present invention provides a chewing gumcomposition comprising: (a) one or more cannabinoids, wherein thecannabinoids are present at less than 15% by weight; and (b) greaterthat 85% by weight gum base. In some embodiments, the gum furthercomprises a shell, wherein the shell encompasses the gum base. In someembodiments, the shell comprises cannabinoids. In some embodiments, thecannabinoids are complexed with an additional agent to enhance one ormore of solubility or absorption. In some embodiments the cannabinoidsare complexed with a cyclodexrin compound. In some embodiments, the oneor more cannabinoids comprise a concentrate as provided above. In someembodiments, concentrate comprises one or more terpenoids as describedabove.

In some embodiments, the present invention provides a cannabinoiddelivery system comprising one or more cannabinoid compounds embedded ina polymer-based thin film, wherein the polymer-based thin film isconfigured to dissolve upon contacting oral mucosa. In some embodiments,the cannabinoid compounds are complexed with a cyclodextrin compound. Insome embodiments, a base polymer, comprising one or more of hydroxypropyl methyl cellulose, hydroxy propyl cellulose, starch, pullulan,pectin, and gelatin comprises at least 35% of the thin film. In someembodiments, the delivery systems further comprise one or moreadditional components alter the mucoadhesion, flexibility, or rate ofdissolving of the thin film. In some embodiments, the one or morecannabinoids comprise a concentrate as provided above. In someembodiments, concentrate comprises one or more terpenoids as describedabove.

In some embodiments, the present invention provides methods of rapidlydelivering a dose of cannabinoid to the bloodstream of a subjectcomprising: (a) placing a cannabinoid delivery system as described aboveon the oral mucosa of the subject; and (b) allowing the thin film of thedelivery system to dissolve, thereby releasing a dose on cannabinoidonto the oral mucosa. In some embodiments, the dose comprises 2-200 mgof cannabinoid.

In some embodiments, the present invention provides for use of aconcentrate, cannabinoid delivery system, oral delivery vehicle, topicalskin care product, dietary supplement, chewing gum or food product asdescribed above to reduce inflammation, reduce pain, reduce nausea,enhance mood, produce a calm feeling, induce drowsiness or sleep, reduceanxiety, support joint health, support mental health, supportanti-inflammatory response by the body, support brain function, supportfeelings of wellbeing, support healthy skin and reduce blemishes.

In some embodiments, the present invention provides methods of reducinginflammation, reducing pain, reducing nausea, enhancing mood, producinga calm feeling, inducing drowsiness or sleep, reducing anxiety,supporting joint health, supporting mental health, supportinganti-inflammatory response by the body, support braining function,supporting feelings of wellbeing, supporting healthy skin or reduceblemishes in a subject comprising administering an effective amount of aconcentrate, cannabinoid delivery system, oral delivery vehicle, dietarysupplement, chewing gum or food product as described above.

The present invention further relates to extracts concentrates obtainedfrom extraction from Cannabis, preferably cannabinoid and/or terpeneconcentrates, wherein THC is converted to one or more natural CBN-typecannabinoids by an oxidizing treatment. The extracts and concentratesfind use for direct vaporization, infusion into edible matrices,infusion into topical skin care products, in electronic inhalationdevices, and as nutraceuticals. The present invention relates toextracts concentrates obtained from extraction from Cannabis, preferablycannabinoid and/or terpene concentrates, wherein THC is converted to oneor more natural CBN-type cannabinoids by an oxidizing treatment. Theextracts and concentrates find use for direct vaporization, infusioninto edible matrices, in electronic inhalation devices, and asnutraceuticals.

In some embodiments, the present invention provides methods ofconverting THC in a THC extract to CBN comprising: (a) contacting theTHC extract with an oxidizing agent under conditions such that THC isoxidized to CBN; and (b) allowing sufficient time for the oxidizingagent to react with the THC extract such that THC is converted to one ormore CBN-type cannabinoids to provide a converted-CBN extract. In someembodiments, the THC is in an organic solvent. In some embodiments, themethods further comprise a step between steps (a) and (b) ofdecarboxylating THC(a) present in the THC-rich extract to yieldadditional THC. In some embodiments, step (c) is performed underexposure to UV light and in the presence of an oxygen source. In someembodiments, the oxidizing agent is selected from the group consistingof hydrogen peroxide, ozone, halogens, sulfuric acid, peroxydisulfuricacid, permamnganate compounds, and nitrous oxide. In some embodiments,from about 10 to about 95% of THC in the THC extract is converted to aCBN-type cannabinoid.

In some embodiments, the THC extract is a THC concentrate. In someembodiments, the THC concentrate is prepared by: (a) concentratingglandular trichomes from Cannabis plant material; (b) passing a solventthough the plant material to produce a cannabinoid/terpenoid-containingeluate; (c) filtering solids from the eluate; and (d) refining theeluate to remove undesirable impurities.

In some embodiments, the THC extract is co-enriched for one or moreterpenoids. In some embodiments, the one or more terpenoids are selectedfrom the group consisting of Alloaromadendrene, allyl hexanoate,benzaldehyde, (Z)-α-cis-bergamotene, (Z)-α-trans-bergamotene,β-bisabolol, epi-α-bisabolol, β-bisabolene, borneol (camphol),cis-γ-bisabolene, borneol acetate (bornyl acetate), α-cadinene,camphene, camphor, cis-carveol, caryophyllene (β-caryophyllene),α-humulene (α-caryophyllene), γ-cadinene, Δ-3-carene, caryophylleneoxide, 1,8-cineole, citral A, citral B, cinnameldehyde, α-copaene(aglaiene), γ-curcumene, O-cymene, β-elemene, γ-elemene, ethyldecdienoate, ethyl maltol, ethyl propionate, ethylvanillin, eucalyptol,α-eudesmol, β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene((Z)-β-farnesene), trans-α-farnesene, trans-β-farnesene, trans-γbisabolene, fenchone, fenchol (norbornanol, β-fenchol), geraniol,α-guaiene, guaiol, methyl anthranilate, methyl salicylate,2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol,isoamyl acetate, lemenol, limonene, d-limonene (limonene), linolool(linalyl alcohol, β-linolool), α-longipinene, menthol, γ-muurolene,myrcene (β-myrcene), nerolidol, trans-nerolidol, nerol, β-ocimene(cis-ocimene), octyl acetate, α-phellandrene, phytol, α-pinene(2-pinene), β-pinene, pulegone, sabinene, cis-sabinene hydrate(cis-thujanol), β-selinene, α-selinene, γ-terpinene, terpinolene(isoterpine), terpineol (a terpineol), terpineol-4-ol, α-terpinene(terpilene), α-thujene (origanene), vanillin, viridiflorene (ledene),α-ylangene.

In some embodiments, the methods further comprise the step offormulating the CBN-converted extract with a nutraceutically orpharmaceutically acceptable carrier. In some embodiments, the methodsfurther comprise combining the CBN-converted extract with one or morebioactive agents, nutraceutical agents, or phytonutrients. In someembodiments, the one or more bioactive agents, nutraceutical agents, orphytonutrients is from a source other than Cannabis. In someembodiments, the methods further comprise incorporating theCBN-converted extract into an oral delivery vehicle selected from thegroup consisting of a tablet, capsule, chewable matrix, dissolvablefilm, and chewing gum. In some embodiments, the methods further compriseincorporating the CBN-converted extract into a vaporizable formulation.

In some embodiments, the present invention provides a converted-CBNconcentrate produced by the processes described above.

In some embodiments, the present invention provides a convertedCBN-concentrate comprising at least 20% of one or more CBN-typecannabinoids selected from the group consisting of Cannabinol CBN-C5,Cannabinol-C4 CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2,Cannabiorcol CBN-C1, Cannabinolic acid A CBNA-C5 A, and Cannabinolmethyl ether CBNM-C5. In some embodiments, the concentrate comprises atleast 30% of one or more CBN-type cannabinoids selected from the groupconsisting of Cannabinol CBN-C5, Cannabinol-C4 CBN-C4, CannabivarinCBN-C3, Cannabinol-C2 CBN-C2, Cannabiorcol CBN-C1, Cannabinolic acid ACBNA-C5 A, and Cannabinol methyl ether CBNM-C5. In some embodiments, theconcentrate comprises at least 50% of one or more CBN-type cannabinoidsselected from the group consisting of Cannabinol CBN-C5, Cannabinol-C4CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2, Cannabiorcol CBN-C1,Cannabinolic acid A CBNA-C5 A, and Cannabinol methyl ether CBNM-C5. Insome embodiments, the concentrate comprises at least 70% of one or moreCBN-type cannabinoids selected from the group consisting of CannabinolCBN-C5, Cannabinol-C4 CBN-C4, Cannabivarin CBN-C3, Cannabinol-C2 CBN-C2,Cannabiorcol CBN-C1, Cannabinolic acid A CBNA-C5 A, and Cannabinolmethyl ether CBNM-C5. In some embodiments, the concentrate comprises atleast 90% of one or more CBN-type cannabinoids selected from the groupconsisting of Cannabinol CBN-C5, Cannabinol-C4 CBN-C4, CannabivarinCBN-C3, Cannabinol-C2 CBN-C2, Cannabiorcol CBN-C1, Cannabinolic acid ACBNA-C5 A, and Cannabinol methyl ether CBNM-C5.

In some embodiments, the concentrate further comprises at least 1% of atleast a second cannabinoid selected from the group consisting ofCannabigerol (E)-CBG-C5, Cannabigerol monomethyl ether (E)-CBGM-C5 A,Cannabigerolic acid A (Z)-CBGA-C5 A, Cannabigerovarin (E)-CBGV-C3,Cannabigerolic acid A (E)-CBGA-C5 A, Cannabigerolic acid A monomethylether (E)-CBGAM-C5 A and Cannabigerovarinic acid A (E)-CBGVA-C3 A);(±)-Cannabichromene CBC-C5, (±)-Cannabichromenic acid A CBCA-C5 A,(±)-Cannabivarichromene, (±)-Cannabichromevarin CBCV-C3,(±)-Cannabichromevarinic acid A CBCVA-C3 A); (−)-Cannabidiol CBD-C5,Cannabidiol momomethyl ether CBDM-C5, Cannabidiol-C4 CBD-C4,(−)-Cannabidivarin CBDV-C3, Cannabidiorcol CBD-C1, Cannabidiolic acidCBDA-C5, Cannabidivarinic acid CBDVA-C3); Cannabinodiol CBND-C5,Cannabinodivarin CBND-C3), (−)-(9R,10R)-trans-Cannabitriol(−)-trans-CBT-C5, (+)-(9S,10S)-Cannabitriol (+)-trans-CBT-C5,(±)-(9R,10S/9S,10R)—); Cannabitriol (±)-cis-CBT-C5,(−)-(9R,10R)-trans-10-O-Ethyl-cannabitriol (−)-trans-CBT-OEt-C5,(±)-(9R,10R/9S,10S)-Cannabitriol-C3(±)-trans-CBT-C3,8,9-Dihydroxy-Δ6a(10a)-tetrahydrocannabinol8,9-Di-OH-CBT-C5, Cannabidiolic acid A cannabitriol ester CBDA-C59-OH-CBT-C5 ester,(−)-(6aR,9S,10S,10aR)-9,10-Dihydroxy-hexahydrocannabinol, Cannabiripsol,Cannabiripsol-C5, (−)-6a,7,10a-Trihydroxy-Δ9-tetrahydrocannabinol(−)-Cannabitetrol, 10-Oxo-Δ6a(10a)tetrahydrocannabinol OTHC);(5aS,6S,9R,9aR)-Cannabielsoin CBE-C5, (5aS,6S,9R,9aR)—C3-CannabielsoinCBE-C3, (5aS,6S,9R,9aR)-Cannabielsoic acid A CBEA-C5 A,(5aS,6S,9R,9aR)-Cannabielsoic acid B CBEA-C5 B;(5aS,6S,9R,9aR)—C3-Cannabielsoic acid B CBEA-C3 B,Cannabiglendol-C30H-iso-HHCV-C3, Dehydrocannabifuran DCBF-C5,Cannabifuran CBF-C5), (−)-Δ7-trans-(1R,3R,6R)-Isotetrahydrocannabinol,(±)-Δ7-1,2-cis-(1R,3R,6S/1S,3S,6R)-Isotetrahydrocannabivarin,(−)-Δ7-trans-(1R,3R,6R)-Isotetrahydrocannabivarin);(±)-(1aS,3aR,8bR,8cR)-Cannabicyclol CBL-C5,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclolic acid A CBLA-C5 A,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclovarin CBLV-C3; Cannabicitran CBT-C5);Cannabichromanone CBCN-C5, Cannabichromanone-C3 CBCN-C3, andCannabicoumaronone CBCON-C5). In some embodiments, the concentratecomprises at least 1% w/w of two of the cannabinoid compounds. In someembodiments, the concentrate comprises at least 1% w/w of three of thecannabinoid compounds. In some embodiments, the concentrate comprises atleast 1% w/w of four of the cannabinoid compounds. In some embodiments,the concentrate comprises at least 1% w/w of five of the cannabinoidcompounds.

In some embodiments, the concentrate is further co-enriched for at least0.1% w/w of at least one terpenoid selected from the group consisting ofAlloaromadendrene, allyl hexanoate, benzaldehyde, (Z)-α-cis-bergamotene,(Z)-α-trans-bergamotene, β-bisabolol, epi-α-bisabolol, β-bisabolene,borneol (camphol), cis-γ-bisabolene, borneol acetate (bornyl acetate),α-cadinene, camphene, camphor, cis-carveol, caryophyllene(β-caryophyllene), α-humulene (α-caryophyllene), γ-cadinene, Δ-3-carene,caryophyllene oxide, 1,8-cineole, citral A, citral B, cinnameldehyde,α-copaene (aglaiene), γ-curcumene, β-cymene, β-elemene, γ-elemene, ethyldecdienoate, ethyl maltol, ethyl propionate, ethylvanillin, eucalyptol,α-eudesmol, β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene((Z)-β-farnesene), trans-α-farnesene, trans-β-farnesene, trans-γbisabolene, fenchone, fenchol (norbornanol, β-fenchol), geraniol,α-guaiene, guaiol, methyl anthranilate, methyl salicylate,2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol,isoamyl acetate, lemenol, limonene, d-limonene (limonene), linolool(linalyl alcohol, β-linolool), α-longipinene, menthol, γ-muurolene,myrcene (β-myrcene), nerolidol, trans-nerolidol, nerol, β-ocimene(cis-ocimene), octyl acetate, α-phellandrene, phytol, α-pinene(2-pinene), β-pinene, pulegone, sabinene, cis-sabinene hydrate(cis-thujanol), β-selinene, α-selinene, γ-terpinene, terpinolene(isoterpine), terpineol (α terpineol), terpineol-4-ol, α-terpinene(terpilene), α-thujene (origanene), vanillin, viridiflorene (ledene),α-ylangene. In some embodiments, the concentrate comprises at least 0.1%of two of the terpenoids. In some embodiments, the concentrate comprisesat least 0.1% of three of the terpenoids. In some embodiments, theconcentrate comprises at least 0.1% of four of the terpenoids. In someembodiments, the concentrate comprises at least 0.1% of five of theterpenoids.

In some embodiments, the concentrates comprise a total cannabinoidfraction of from about 45% to 98% w/w (calculated as a weight percentageof the total weight of the concentrate), most preferably about 65% to95% w/w total CBN-type compounds (e.g., as listed above) and a totalterpenoid fraction of from about 0.1% to 5% w/w total terpenoids (e.g.,as listed above; calculated as a weight percentage of the total weightof the concentrate). In some embodiments, the total cannabinoid fractioncontains from about 62% to about 92% w/w or from about 75% to 92% w/wCBN-type compounds (calculated as a weight percentage of the totalweight of the concentrate). As described above, the total cannabinoidfraction may additionally comprise at least 1%, 2%, 5%, or 10% w/w ofthree or more of the cannabinoid compounds (calculated as a weightpercentage of the total weight of the concentrate). In some embodiments,the concentrate comprises at least 1%, 2%, 5%, or 10% w/w of four ormore of the cannabinoid compounds (calculated as a weight percentage ofthe total weight of the concentrate). In some embodiments, theconcentrate comprises at least 1%, 2%, 5%, or 10% w/w of five or more ofthe cannabinoid compounds. Likewise, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w oftwo or more of the terpenoids (calculated as a weight percentage of thetotal weight of the concentrate). In some embodiments, the totalterpenoid fraction may additionally comprise at least 0.01%, 0.05%,0.1%, 0.2%, or 0.5% w/w of three or more of the terpenoids (calculatedas a weight percentage of the total weight of the concentrate). In someembodiments, the total terpenoid fraction may additionally comprise atleast 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of four or more of theterpenoids (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w offive or more of the terpenoids (calculated as a weight percentage of thetotal weight of the concentrate). In some embodiments, the totalterpenoid fraction may additionally comprise at least 0.01%, 0.05%,0.1%, 0.2%, or 0.5% w/w of ten or more of the terpenoids (calculated asa weight percentage of the total weight of the concentrate). It shouldbe noted that in defining the concentrates in weight percentage terms,the weight percentage of the combined components will not exceed 100%.It should be noted that in defining the concentrates in weightpercentage terms, the weight percentage of the combined components willnot exceed 100%.

In some embodiments, the concentrate is substantially free of THC-typecompounds.

In some embodiments, the present invention provides an oral deliveryvehicle comprising a concentrate as described above.

In some embodiments, the present invention provides a chewing gumcomprising a concentrate as described above.

In some embodiments, the present invention provides an oral deliveryvehicle comprising a concentrate as described above.

In some embodiments, the present invention provides a dietary supplementcomprising a concentrate as described above.

In some embodiments, the present invention provides a food productcomprising a concentrate as described above.

In some embodiments, the present invention provides a thin film deliveryvehicle comprising a concentrate as described above.

In some embodiments, the present invention provides a compositioncomprising a concentrate as described in combination with one or morebioactive agents, nutraceutical agents, phytonutrients, orpharmaceutically acceptable carriers and combinations thereof.

In some embodiments, the present invention provides for use of aconcentrate, cannabinoid delivery system, oral delivery vehicle, dietarysupplement, chewing gum, food product or composition as described aboveto ameliorate the psychoactive responses produced by other cannabinoids,reduce inflammation, reduce pain, reduce pain associated with cancer,reduce neuropathic pain, reduce nausea, enhance mood, produce a calmfeeling, induce drowsiness or sleep, reduce anxiety, support jointhealth, support mental health, support anti-inflammatory response by thebody, support brain function, support feelings of wellbeing, supporthealthy skin and reduce blemishes.

In some embodiments, the present invention provides methods ofameliorating psychoactive responses produced by other cannabinoids,reducing inflammation, reducing pain, reducing nausea, enhancing mood,producing a calm feeling, inducing drowsiness or sleep, reducinganxiety, supporting joint health, supporting mental health, supportinganti-inflammatory response by the body, supporting brain function,supporting feelings of wellbeing, supporting healthy skin or reducingblemishes in a subject comprising administering an effective amount of aconcentrate, cannabinoid delivery system, oral delivery vehicle, dietarysupplement, chewing gum or food product as described above.

Definitions

As used herein the term “Cannabis” is used to refer to plants of thegenus Cannabis, including Cannabis sativa, Cannabis indica, and Cannabisruderalis.

As used herein, the terms “trichome” and “glandular trichome” are usedinterchangeably to refer to plant epidermal structures that comprisesecretions produced by the plant.

As used herein, the term “cannabinoid” refers to a chemical compoundthat shows direct or indirect activity at a cannabinoid receptor. Thereare two main cannabinoid receptors, CB₁ and CB₂. Other receptors thatresearch suggests have cannabinoid activity include the GPR55 and GPR 18receptors. The term “phytocannabinoid” refers to cannabinoids that occurin a plant species or are derived from cannabinoids occurring in a plantspecies. Examples of cannabinoids include, but are not limited to,Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinol (CBN),Cannabigerol (CBG), Cannabichromene (CBC), Cannabicyclol (CBL),Cannabivarin (CBV), Tetrahydrocannabivarin (THCV), Cannabidivarin(CBDV), Cannabichromevarin (CBCV), Cannabigerovarin (CBGV), CannabigerolMonomethyl Ether (CBGM). Examples of structures of cannabinoids include,but are not limited to:

As used herein, the term “terpene” refers to hydrocarbons of biologicalorigin having carbon skeletons formally derived from isoprene[CH2=C(CH3)CH═CH2]. This class is subdivided into the C5 hemiterpenes,C10 monoterpenes, C15 sesquiterpenes, C20 diterpenes, C25sesterterpenes, C30 triterpenes, C40 tetraterpenes (carotenoids), andC5n polyterpenes.

As used herein, the term “terpenoid” refers to hydrocarbons ofbiological origin having carbon skeletons formally derived from isoprene[CH2=C(CH3)CH═CH2] and differing from terpenes in that one or moremethyl groups have been moved or added, or an oxygen added compared tothe terpene. Terpenoids are classified as follows: Hemiterpenoids, 1isoprene unit (5 carbons); Monoterpenoids, 2 isoprene units (10C);Sesquiterpenoids, 3 isoprene units (15C); Diterpenoids, 4 isoprene units(20C) (e.g. ginkgolides); Sesterterpenoids, 5 isoprene units (25C);Triterpenoids, 6 isoprene units (30C) (e.g. sterols); Tetraterpenoids, 8isoprene units (40C) (e.g. carotenoids); and Polyterpenoids (largernumber of isoprene units). Examples of terpenoids found in Cannabisinclude, but are not limited to, Limonene, α-Pinene, β-Myrcene,Linolool, β-Caryophyllene, Carophyllene oxide, Nerolidol, and Phytol.

As used herein, the term “solvent extract” refers to a compositionprovided by solvent extraction of a starting material such as Cannabisplant material or trichomes. The solvent extract may preferably have thesolvent substantially removed from the extract, for example byevaporation.

As used herein, the term “enriched for” when used in reference to acomposition means that one or more specified compounds are present in ahigher concentration, commonly expressed as a weight/weight percentage,as compared to a starting material, such as Cannabis plant material ortrichomes.

As used herein the term “concentrate” when used in reference to acomposition containing one or more compounds means that the one or morecompounds are concentrated in the composition on a weight/weight basisas compared to a starting material, such as Cannabis plant material ortrichomes.

As used herein, the term “substantially free of THC-type compounds”refers to extracts, fractions or other preparations from a Cannabisplant that contain less than 2%, preferably less than 1%, morepreferably less than 0.5%, and most preferably less than 0.1%Tetrahydrocannabinol-type (THC) compounds (e.g., Δ⁹-TetrahydrocannabinolΔ⁹-THC-C₅, Δ⁹-Tetrahydrocannabinol-C₄, Δ⁹-THC-C₄,Δ⁹-Tetrahydrocannabivarin Δ⁹-THCV-C₃, Δ⁹-TetrahydrocannabiorcolΔ⁹-THCO-C₁, Δ⁹-Tetrahydrocannabinolic acid A Δ⁹-THCA-C₅ A,Δ⁹-Tetrahydrocannabinolic acid B, Δ⁹-THCA-C₅ B,Δ⁹-Tetrahydrocannabinolic acid-C₄ A and/or B Δ⁹-THCA-C₄ A and/or B,Δ⁹-Tetrahydro-cannabivarinic acid A Δ⁹-THCVA-C₃ A,Δ⁹-Tetrahydrocannabiorcolic acid A and/or B Δ⁹-THCOA-C₁ A and/or B),(−)-Δ⁸-trans-(6aR,10aR)-Δ⁸-Tetrahydrocannabinol Δ⁸-THC-C₅,(−)-Δ⁸-trans-(6aR,10aR)-Tetrahydrocannabinolic acid A Δ⁸-THCA-C₅ A,(−)-(6aS,10aR)-Δ⁹-Tetrahydrocannabinol (−)-cis-Δ⁹-THC-C₅).

As used herein, the term “phytonutrient” refers to organic compoundsisolated from plants that have a biological effect, and includes, but isnot limited to, compounds of the following classes: cannabinoids,isoflavonoids, oligomeric proanthcyanidins, indol-3-carbinol,sulforaphone, fibrous ligands, plant phytosterols, ferulic acid,anthocyanocides, triterpenes, omega 3/6 fatty acids, polyacetylene,quinones, terpenes, cathechins, gallates, and quercitin.

As used herein, the term “functional foods” refers to food products thatinclude biologically active nutraceutical agents.

As used herein, the terms “nutraceutical agent,” and related terms,refer to natural, bioactive chemical compounds that have healthpromoting, disease preventing or medicinal properties. Examples ofnutraceutical agents include, but are not limited to, extracts fromAllium Cepa, Allium Sativum, Aloe Vera, Angelica Species, NaturallyOccurring Antioxidants, Aspergillus Oryzae Enzyme Therapy, barley grass,Bromelain, Carnitine, Carotenoids and Flavonoids, Catechin, CentellaAsiatica (Gotu kola), Coenzyme Q10, Chinese Prepared Medicines, ColeusForskohlii, Commiphora Mukul, Crataegus Oxyacantha (Hawthorne), CurcumaLonga (Turmeric), Echinacea Species (Purple Coneflower), EleutherococcusSenticosus (Siberian Ginseng), Ephedra Species, Dietary Fish OilConsumption and Fish Oil Supplementation, Genistein, Ginkgo Biloba,Glycyrrhiza (Licorice), Hypericum Perforatum (St. John's Wort),Hydrastis (Goldenseal) and Other Berberine-Containing Plants,Lactobacillus, Lobelia (Indian Tobacco), Melaleuca Alternifolia, MenthaPiperita, NGNA, Panax Ginseng, Pancreatic Enzymes, Piper Mythisticum,Procyanidolic Oligomers, Pygeum Africanum, Quercetin, SarsaparillaSpecies, Serenoa Repens (Saw palmetto, Sabal serrulata), SilybumMarianum (Milk Thistle), Rosemary/Lemon balm, Selenite, TabebuiaAvellanedae (LaPacho), Taraxacum Officinale, Tanacetum Parthenium(Feverfew), Taxol, Uva Ursi (Bearberry), Vaccinium Myrtillus(Blueberry), Valerian Officinalis, Viscum Album (Mistletoe), Vitamin A,Beta-Carotene and Other Carotenoids, and Zingiber Officinale (Ginger).

As used herein, the terms “subject” and “patient” refer to any animal,such as a mammal like a dog, cat, bird, livestock, and preferably ahuman. Specific examples of “subjects” and “patients” include, but arenot limited to, individuals suffering from viral obesity.

As used herein, the term “physiologically acceptable carrier” refers toany carrier or excipient commonly used with oily pharmaceuticals. Suchcarriers or excipients include, but are not limited to, oils, starch,sucrose and lactose.

As used herein, the term “oral delivery vehicle” refers to any means ofdelivering a pharmaceutical orally, including, but not limited to,capsules, pills, tablets and syrups.

As used herein, the term “food product” refers to any food or feedsuitable for consumption by humans, non-ruminant animals, or ruminantanimals. The “food product” may be a prepared and packaged food (e.g.,mayonnaise, salad dressing, bread, or cheese food) or an animal feed(e.g., extruded and pelleted animal feed or coarse mixed feed).“Prepared food product” means any pre-packaged food approved for humanconsumption.

As used herein, the term “foodstuff” refers to any substance fit forhuman or animal consumption.

As used herein, the term “dietary supplement” refers to a small amountof a compound for supplementation of a human or animal diet packaged insingle or multiple dose units. Dietary supplements do not generallyprovide significant amounts of calories but may contain othermicronutrients (e.g., vitamins or minerals).

As used herein, the term “nutritional supplement” refers to acomposition comprising a “dietary supplement” in combination with asource of calories. In some embodiments, nutritional supplements aremeal replacements or supplements (e.g., nutrient or energy bars ornutrient beverages or concentrates).

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to extracts and concentrates obtained fromextraction from Cannabis, preferably cannabinoid and/or terpeneconcentrates, and formulation of the concentrates, particularly for usefor direct vaporization, infusion into edible matrices, in electronicinhalation devices, and as nutraceuticals. The concentrates describedherein may preferably be produced from either drug or industrialCannabis species. The concentrates are preferably enriched for one ormore cannabinoids and/or terpenes as described in more detail below. Theconcentrates may be formulated in a variety of ways, with or withoutother phytonutrients or nutraceutical agents as also described in moredetail below.

Disclosed herein are efficient methods to produce Cannabis extracts withunique chemical properties using mechanical extraction followed by asolvent extraction. The extracts are then optionally processed by awhipping procedure to produce a finished extract with unique chemicaland physical properties. The two-step extraction has many advantagesover other techniques. The process allows for a higher throughput withless solvent waste because of the ability to obtain a much larger amountof finished extract from each solvent extraction pass. The finalextracts are of a higher quality containing less water, chlorophyll, andother unwanted contaminants found in solvent extracts made directly fromplant materials. The final extracts are also more visually appealingbecause of their lighter color. Another advantage is to allow for thefirst extraction to take place on fresh or freshly dried Cannabis afterwhich the crude extract can be stored for great lengths of time before asolvent extraction takes place. Other methods produce a lower qualityextract when significant time passes between the harvesting of the plantmaterial and when it is processed.

The present invention further relates to extracts concentrates obtainedfrom extraction from Cannabis, preferably cannabinoid and/or terpeneconcentrates, wherein THC is converted to one or more natural CBN-typecannabinoids by an oxidizing treatment. The extracts and concentratesfind use for direct vaporization, infusion into edible matrices, inelectronic inhalation devices, and as nutraceuticals. The presentinvention relates to extracts concentrates obtained from extraction fromCannabis, preferably cannabinoid and/or terpene concentrates, whereinTHC is converted to one or more natural CBN-type cannabinoids by anoxidizing treatment. The extracts and concentrates find use for directvaporization, infusion into edible matrices, in electronic inhalationdevices, and as nutraceuticals. The concentrates described herein maypreferably be produced from either drug or industrial Cannabis species.The concentrates are preferably enriched for one or more cannabinoids,preferably CBN-type cannabinoids, and/or terpenes as described in moredetail below. The concentrates may be formulated in a variety of ways,with or without other phytonutrients or nutraceutical agents as alsodescribed in more detail below.

Disclosed herein are efficient methods to produce Cannabis extracts withunique chemical properties using mechanical extraction followed by asolvent extraction and oxidation process. The extracts are thenoptionally processed by a whipping procedure to produce a finishedextract with unique chemical and physical properties. The two-stepextraction has many advantages over other techniques. The process allowsfor a higher throughput with less solvent waste because of the abilityto obtain a much larger amount of finished extract from each solventextraction pass. The final extracts are of a higher quality containingless water, chlorophyll, and other unwanted contaminants found insolvent extracts made directly from plant materials. The final extractsare also more visually appealing because of their lighter color. Anotheradvantage is to allow for the first extraction to take place on fresh orfreshly dried Cannabis after which the crude extract can be stored forgreat lengths of time before a solvent extraction takes place. Othermethods produce a lower quality extract when significant time passesbetween the harvesting of the plant material and when it is processed.

Cannabis produces the majority of its active ingredients (cannabinoidsand terpenoids) in glandular trichomes found on the flowers, buds,leaves, and stalks of the plants. In preferred embodiments of thepresent invention, Cannabis plant material (e.g., flowers and leaves,either fresh or dried) containing glandular trichomes are processedmechanically to remove and concentrate the majority of these trichomes.Preferred processes separate the trichomes from the plant material bypassing the trichomes through a mesh of appropriate size to allow thetrichomes to pass through and exclude as much unwanted plant material aspossible. The mesh may be made of any suitable material, e.g., stainlesssteel, aluminum, nylon, etc. Different varieties of Cannabis producetrichome heads of varying size, thus the optimal mesh size depends onthe average size of the trichome heads being collected. In preferredembodiments, the processes of the present invention utilize mesh sizesranging from 1 to 1000 microns in diameter, most preferably from 1 to350 microns in diameter. One or multiple layers of mesh may be utilized.The use of multiple layers of mesh can help to further separate thedesired trichomes from unwanted particles of plant material that areeither slightly smaller or slightly larger.

In some embodiments, the mechanical trichome concentration processesutilize a cylindrical mesh drum driven by a belt and motor. The plantmaterial is placed in the drum, the drum is rotated, and the trichomesare expelled from the drum through the mesh pores. In some embodiments,the plant material is frozen (i.e., at −20 C to −70 C) prior totumbling. In some embodiments, the plant material is tumbled in thepresence of ice, preferably dry ice. In some embodiments, the mesh drumis rotated in an ice water bath. Both the dry and wet method yieldtrichome concentrates with high levels of bioactive compounds. When awet process is used, excess liquid is preferably pressed from thetrichome concentrate followed by drying.

The second step in the extraction process comprises solvent extractionof the trichome concentrate. Extracts are preferably produced using asolvent recovery apparatus. For gaseous organic solvent mixtures, apressurized closed botanical extraction system is preferred. For carbondioxide extraction, a supercritical or subcritical botanical extractionapparatus is preferred. For liquid organic solvent extraction, spraydryers and/or common vacuum distillation apparatuses are preferred. Inpreferred embodiments, the apparatus allows for as low temperatureremoval of solvents as possible to avoid unwanted decarboxylation and/orremoval of terpene compounds from the extract.

In all methods, the solvent passes through the trichome concentrateeither in a column packed with the trichome concentrate (as part of thesolvent recovery apparatus or with a discrete step) or the trichomeconcentrate can be saturated with solvent for a defined amount of timefollowed by filtration. Optionally, the extraction can be assistedthrough the use of sonication, microwave assistance, mechanical mixing,or other similar processes.

Examples of useful extraction solvents include gaseous solvents, in aliquid state, either neat or as a mixture, such as propane, n butane,isobutylene and/or isobutane. Examples of preferred solvent mixturesinclude 40-80% isobutane, 60-10% propane, and 20-5% n butane. Othermixtures can reverse these ratios. Examples of preferred liquid (normalT and P) extraction solvents include pentane, isopentane, hexanes (allstructural isomers), ethyl acetate, ethanol, isopropanol, and heptanes(all structural isomers). Carbon dioxide in a supercritical orsubcritical state is also a preferred solvent for the processes of thepresent invention. Other preferred solvent extraction mixtures includemixtures of isobutane and/or pentane with liquid nitrogen passed throughthe plant material followed by an optional sieve with pore diametersfrom 50 to 1000 microns.

After the solvent has been passed through the plant material, a filteror several filter steps can optionally be performed to avoid passingplant material from the crude extract into the final elute. Thefilter(s) can take many forms and have a wide range of pore sizes.Preferred filters include, but are not limited to, Teflon filters,sintered glass, paper, metal mesh, and the like.

Additional bioactive compounds, phytonutrients, nutraceutical agents,flavoring agents and the like may be added to the Cannabis solventextract either before or after solvent removal and concentration.Examples of additives include, but are not limited to, terpene/terpenoidcompounds, other essential oils, natural or artificial flavorings,edible or food grade carrier solvents such as propylene glycol,glycerin, triacetin, food oils, topical oils and butters, etc. Additivesare described in more detail below. Solubilizers, suspension agents, anduptake promoters such as beta-cyclodextrins may also be added before orafter solvent removal.

In preferred embodiments, solvent is removed from the solvent extract toprovide a concentrate. Suitable processes for solvent removal include,but are not limited to, solvent exchange, vacuum distillation, vacuumdesiccation, TFE, or crystallization of active ingredients. Solventremoval may take place at a wide range of temperatures consistent withthe process used.

The extracts can optionally be further processed to concentrate desiredbioactive agents or remove undesired compounds (e.g., contaminants). Insome embodiments, the extract or eluate is passed through a preparatoryor industrial scale column with stationary phases, for example, silica,alumina, C8, or C18 stationary phases. A number of solvent matrices maybe utilized. Gradients may optionally be used to alter the polarity ofmobile phases to facilitate this step. Examples of preferred systemsinclude mixtures of hexane(s), heptane(s), pentane(s), ethyl acetate,and/or ethanol. Fractions can be collected containing desired compounds,and combined if desired. The solvent is then removed as described above.

In some embodiments, target compounds (either desired or undesired) areremoved from solution by crystallization. Crystallization comprisesconcentrating the eluate (with an additional optional solvent exchange)to a preferably non polar solvent (e.g., heptane(s), hexane(s),pentane(s)). The concentrated solvent/extract mixture can be cooled to−20 to −200 C to facilitate crystallization. Optional crystallizationinitiators may be incorporated into the process. Once crystallizationhas occurred, the crystals are filtered and depending on whether theeluate or crystal products are desired, one or the other can bediscarded and desired product can be passed through to additional stepsfor further processing or used as a final product.

In some embodiments, the extract or extract is further refined prior tofinal processing. In some embodiments, the extract is vacuum distilledto near dryness then taken up in ethanol or another alcohol or polarsolvent (the solvent solution may be optionally heated). The ethanolsolution is cooled overnight to −20 C+/−20 degrees after whichundesirable fats, lipids and waxes will precipitate out of the solutionand can be filtered using common methods. In some embodiments,chlorophyll which provides a slight greenish to black hue, is removedfrom the extract. In these embodiments, the extract is taken up in asolvent then exposed to UV light for 30 minutes to 24 hours to breakdown remaining chlorophyll, which will turn from green to amber colors.If the color is still not desirable, activated carbon may be added tothe ethanol solution. Additional solvents may also be utilized. In theseembodiments, the extract and activated carbon are agitated together forseveral hours or days then the extract is filtered out of the activatedcarbon. The solvent may then be removed. In some embodiments, a finalwashing step is beneficial to remove any remaining impurities. In someembodiments, a highly concentrated extract (regardless of the solvent itis dissolved in) is mixed with a non-polar solvent such as pentane,hexane, or heptane. Equal amounts of a concentrated brine solution arethen added. The solution is agitated vigorously then the brine solutionis decanted. This process may preferably be repeated several times. Thisstep may be followed with an optional water wash. The extract may thenbe treated with sodium sulfate or another suitable desiccant to removewater.

In some embodiments, the extract or concentrate obtained as describedabove may be further processed, for example by adding one or morebioactive compounds or nutraceutical agents or by further concentratinga target compound in the Cannabis extract. Further concentration may bepreferably accomplished by column chromatography or crystallization asdescribed above. In some preferred embodiments, the extracts aremechanically processed to provide a composition with desiredphysiochemical properties. In some embodiments, extracts are homogenizedby shear force mixing. Suitable mixing devices include, but are notlimited to, magnetic stir bar apparatuses, wire whisk devices, augers,and the like. Preferably, the extract is mixed (e.g., whisked orwhipped) until dry. The final product preferably has a wax or clay-likeconsistency, is white to slightly yellow in color, and is opaque.

In other embodiments, spray drying is used to provide a fluffycrystalline extract of white to yellow or amber color. In this process,the Cannabis extract is sprayed into a fine mist inside of a vacuumchamber. The system is preferably configured to facilitate theevaporation of solvent from the fine mist leaving behind very finecrystalline cannabinoid extract that can be collected in final formcontaining from 30-99% cannabinoids, preferably from about 55% to 99%cannabinoids, and most preferably from about 65% to 99% cannabinoids. Inother embodiments, thin film evaporation techniques are utilized. Insome embodiments, these methods comprise spreading a thin layer ofconcentrated extract on a surface and placing the surface inside of avacuum oven and/or desiccator. Once the solvent has been removed, awhite to yellow or amber or dark colored extract remains. This extractpreferably has a semicrystalline consistency. This product can be milled(preferably cryogenically milled) to produce a powder or divided intoportions for easy handling.

The extracts described above can preferably be pressed into standardizedpellets through compaction, with or without heat. These pelletspreferably provide a standardized size, weight of cannabinoid extract.The pellets can be packaged in blister pack, plastic jar, or a glassjar.

The concentrates of the present invention are preferably enriched forone or more bioactive compounds from Cannabis. In some embodiments, theconcentrates of the present invention are preferably enriched for one ormore cannabinoids. Preferred cannabinoid compounds include, but are notlimited to: Cannabigerol-type (CBG) compounds (e.g., Cannabigerol(E)-CBG-C₅, Cannabigerol monomethyl ether (E)-CBGM-C₅ A, Cannabigerolicacid A (Z)-CBGA-C₅ A, Cannabigerovarin (E)-CBGV-C₃, Cannabigerolic acidA (E)-CBGA-C₅ A, Cannabigerolic acid A monomethyl ether (E)-CBGAM-C₅ Aand Cannabigerovarinic acid A (E)-CBGVA-C₃ A); Cannabichromene-type(CBC) type compounds (e.g., (±)-Cannabichromene CBC-C₅,(±)-Cannabichromenic acid A CBCA-C₅ A, (±)-Cannabivarichromene,(±)-Cannabichromevarin CBCV-C₃, (±)-Cannabichromevarinic acid A CBCVA-C₃A); Cannabidiol-type (CBD) compounds (e.g., (−)-Cannabidiol CBD-C₅,Cannabidiol momomethyl ether CBDM-C₅, Cannabidiol-C₄ CBD-C₄,(−)-Cannabidivarin CBDV-C₃, Cannabidiorcol CBD-C₁, Cannabidiolic acidCBDA-C₅, Cannabidivarinic acid CBDVA-C₃); Cannabinodiol-type (CBND)compounds (e.g., Cannabinodiol CBND-C₅, Cannabinodivarin CBND-C₃);Tetrahydrocannabinol-type (THC) compounds (e.g., g-TetrahydrocannabinolΔ⁹-THC-C₅, Δ⁹-Tetrahydrocannabinol-C₄, Δ⁹-THC-C₄,Δ⁹-Tetrahydrocannabivarin Δ⁹-THCV-C₃, Δ⁹-Tetrahydrocannabiorcol,Δ⁹-THCO-C₁, Δ⁹-Tetrahydrocannabinolic acid A Δ⁹-THCA-C₅ A,Δ⁹-Tetrahydrocannabinolic acid B, Δ⁹-THCA-C₅ B,Δ⁹-Tetrahydrocannabinolic acid-C₄ A and/or B Δ⁹-THCA-C₄ A and/or B,Δ⁹-Tetrahydro-cannabivarinic acid A Δ⁹-THCVA-C₃ A,Δ⁹-Tetrahydrocannabiorcolic acid A and/or B Δ⁹-THCOA-C₁ A and/or B),(−)-Δ⁸-trans-(6aR,10aR)-Δ⁸-Tetrahydrocannabinol Δ⁸-THC-C₅,(−)-Δ⁸-trans-(6aR,10aR)-Tetrahydrocannabinolic acid A Δ⁸-THCA-C₅ A,(−)-(6aS,10aR)-Δ⁹-Tetrahydrocannabinol (−)-cis-Δ⁹-THC-C₅);Cannabinol-type (CBN) type compounds (e.g., Cannabinol CBN-C₅,Cannabinol-C₄ CBN-C₄, Cannabivarin CBN-C₃, Cannabinol-C₂ CBN-C₂,Cannabiorcol CBN-C₁, Cannabinolic acid A CBNA-C₅ A, Cannabinol methylether CBNM-C₅, (−)-(9R,10R)-trans-Cannabitriol (−)-trans-CBT-C₅,(+)-(9S,10S)-Cannabitriol (+)-trans-CBT-C₅, (±)-(9R,10S/9S,10R)—);Cannabitriol-type (CBT) compounds (e.g., Cannabitriol (±)-cis-CBT-C₅,(−)-(9R,10R)-trans-10-O-Ethyl-cannabitriol (−)-trans-CBT-OEt-C₅,(±)-(9R,10R/9S,10S)-Cannabitriol-C₃ (±)-trans-CBT-C₃,8,9-Dihydroxy-Δ^(6a(10a))-tetrahydrocannabinol 8,9-Di-OH-CBT-C₅,Cannabidiolic acid A cannabitriol ester CBDA-C₅ 9-OH-CBT-C₅ ester,(−)-(6aR,9S,10S,10aR)-9,10-Dihydroxy-hexahydrocannabinol, Cannabiripsol,Cannabiripsol-C₅, (−)-6a,7,10a-Trihydroxy-Δ⁹-tetrahydrocannabinol(−)-Cannabitetrol, 10-Oxo-Δ^(6a(10a))tetrahydrocannabinol OTHC);Cannabielsoin-type (CBE) compounds (e.g., (5 aS,6S,9R,9aR)-CannabielsoinCBE-C₅, (5 aS,6S,9R,9aR)—C₃-Cannabielsoin CBE-C₃, (5aS,6S,9R,9aR)-Cannabielsoic acid A CBEA-C₅ A, (5aS,6S,9R,9aR)-Cannabielsoic acid B CBEA-C₅ B; (5aS,6S,9R,9aR)—C₃-Cannabielsoic acid B CBEA-C₃ B,Cannabiglendol-C₃₀H-iso-HHCV-C₃, Dehydrocannabifuran DCBF-C₅,Cannabifuran CBF-C₅) Isocannabinoids compounds (e.g.,(−)-Δ⁷-trans-(1R,3R,6R)-Isotetrahydrocannabinol,(±)-Δ⁷-1,2-cis-(1R,3R,6S/1S,3S,6R)-Isotetrahydrocannabivarin,(−)-Δ⁷-trans-(1R,3R,6R)-Isotetrahydrocannabivarin); Cannabicyclol-type(CBL) compounds (e.g., (±)-(1aS,3aR,8bR,8cR)-CannabicyclolCBL-C₅,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclolic acid A CBLA-C₅ A,(±)-(1aS,3aR,8bR,8cR)-Cannabicyclovarin CBLV-C₃; Cannabicitran-type(CBT) compounds (e.g., Cannabicitran CBT-C₅); or Cannabichromanone-type(CBCN) compounds (e.g., Cannabichromanone CBCN-C₅, Cannabichromanone-C3CBCN-C₃, Cannabicoumaronone CBCON-C₅). In some embodiments, thecomposition comprise greater than about 0.5%, 1%, 2%, 5%, 10%, 20%, 30%,40%, 50%, 60%, 70%, 80%, 90%, 95% or 99% w/w of one of the foregoingcompounds. In some embodiments, the compositions comprise from 0.5%, 1%,2%, 5%, 10% or 20% w/w to about 25%, 30%, 40% or 50% w/w of one of theforegoing compounds. In some embodiments, the concentrates of thepresent invention are co-enriched for one or more of the foregoingcompounds, for example, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of the compounds.For example, in some embodiments, the concentrates comprise from about0.5%, 1%, 2%, or 5% w/w to about 10% or 20% w/w of a combination of theforegoing compounds. In some embodiments, the compositions areessentially free of THC-type cannabinoid compounds. In some embodiments,the compositions are essentially free of CBN-type compounds. Thus, insome embodiments, the concentrates of the present invention are enriched(as specified by the percentages above) for one or more cannabinoids asdescribed, with the proviso that the cannabinoids are not THC-typecannabinoid or CBN-type cannabinoid. In some embodiments, theconcentrates are enriched for one or more Cannabigerol-type (CBG)compounds; Cannabichromene-type (CBC) type compounds; Cannabidiol-type(CBD) compounds; Cannabinodiol-type (CBND) compounds; Cannabielsoin-type(CBE) compounds; Isocannabinoids compounds; Cannabicyclol-type (CBL)compounds; Cannabicitran-type (CBT) compounds; or Cannabichromanone-type(CBCN) compounds.

In some embodiments, the concentrates of the present invention areco-enriched for one or more cannabinoid compounds (in the combinationsand w/w percentages described above) and one or more terpenoids. Theterpenoids are preferably elected from one or more of alloaromadendrene,allyl hexanoate, benzaldehyde, (Z)-α-cis-bergamotene,(Z)-α-trans-bergamotene, β-bisabolol, epi-α-bisabolol, β-bisabolene,borneol (camphol), cis-γ-bisabolene, borneol acetate (bornyl acetate),α-cadinene, camphene, camphor, cis-carveol, caryophyllene(β-caryophyllene), α-humulene (α-caryophyllene), γ-cadinene, Δ-3-carene,caryophyllene oxide, 1,8-cineole, citral A, citral B, cinnameldehyde,α-copaene (aglaiene), γ-curcumene, β-cymene, β-elemene, γ-elemene, ethyldecdienoate, ethyl maltol, ethyl propionate, ethylvanillin, eucalyptol,α-eudesmol, β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene(O-β-farnesene), trans-α-farnesene, trans-β-farnesene, trans-γbisabolene, fenchone, fenchol (norbornanol, β-fenchol), geraniol,α-guaiene, guaiol, methyl anthranilate, methyl salicylate,2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol,isoamyl acetate, lemenol, limonene, d-limonene (limonene), linolool(linalyl alcohol, β-linolool), α-longipinene, menthol, γ-muurolene,myrcene (β-myrcene), nerolidol, trans-nerolidol, nerol, β-ocimene(cis-ocimene), octyl acetate, α-phellandrene, phytol, α-pinene(2-pinene), β-pinene, pulegone, sabinene, cis-sabinene hydrate(cis-thujanol), β-selinene, α-selinene, γ-terpinene, terpinolene(isoterpine), terpineol (a terpineol), terpineol-4-ol, α-terpinene(terpilene), α-thujene (origanene), vanillin, viridiflorene (ledene),and α-ylange. In some embodiments, the concentrates one or morecannabinoid compounds (in the combinations and w/w percentages describedabove) in combination with from 0.1%, 0.5%, 1%, 2%, 3% to about 5% or10% of one or more of Alloaromadendrene, allyl hexanoate, benzaldehyde,(Z)-α-cis-bergamotene, (Z)-α-trans-bergamotene, β-bisabolol,epi-α-bisabolol, β-bisabolene, borneol (camphol), cis-γ-bisabolene,borneol acetate (bornyl acetate), α-cadinene, camphene, camphor,cis-carveol, caryophyllene (β-caryophyllene), α-humulene(α-caryophyllene), γ-cadinene, Δ-3-carene, caryophyllene oxide,1,8-cineole, citral A, citral B, cinnameldehyde, α-copaene (aglaiene),γ-curcumene, β-cymene, β-elemene, γ-elemene, ethyl decdienoate, ethylmaltol, ethyl propionate, ethylvanillin, eucalyptol, α-eudesmol,β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene ((Z)-β-farnesene),trans-α-farnesene, trans-β-farnesene, trans-γ bisabolene, fenchone,fenchol (norbornanol, β-fenchol), geraniol, α-guaiene, guaiol, methylanthranilate, methyl salicylate, 2-methyl-4-heptanone,3-methyl-4-heptanone, hexyl acetate, ipsdienol, isoamyl acetate,lemenol, limonene, d-limonene (limonene), linolool (linalyl alcohol,β-linolool), α-longipinene, menthol, γ-muurolene, myrcene (β-myrcene),nerolidol, trans-nerolidol, nerol, β-ocimene (cis-ocimene), octylacetate, α-phellandrene, phytol, α-pinene (2-pinene), β-pinene,pulegone, sabinene, cis-sabinene hydrate (cis-thujanol), β-selinene,α-selinene, γ-terpinene, terpinolene (isoterpine), terpineol (aterpineol), terpineol-4-ol, α-terpinene (terpilene), α-thujene(origanene), vanillin, viridiflorene (ledene), and α-ylange.

In some embodiments, the present invention provides concentrates andextracts that are treated to convert THC-type cannabinoids into CBN-typecannabinoids. The concentrates and extracts are preferably produced asdescribed above. In preferred embodiments, the concentrates and extractsare substantially free of THC-type cannabinoids. In some embodiments,the extracts and concentrates comprise less than 5%, 4%, 3%, 2%, 1%,0.5% or 0.1% w/w THC-type cannabinoids. In some embodiments, theextracts and concentrates are enriched for one or more CBN-typecannabinoids. In some embodiments, the CBN-type cannabinoids areselected from Cannabinol CBN-C₅, Cannabinol-C₄ CBN-C₄, CannabivarinCBN-C₃, Cannabinol-C₂ CBN-C₂, Cannabiorcol CBN-C₁, Cannabinolic acid ACBNA-C₅ A, and Cannabinol methyl ether CBNM-C₅. In some embodiments, theconcentrates comprise greater than 20%, 30%, 40%, 50%, 60%, 70%, 80%,90% or 95% w/w of one or more (e.g., 2, 3, 4, or 5) CBN-typecannabinoids. In some embodiments, the concentrates are co-enriched forone or more terpenoids. The terpenoids are preferably selected from oneor more of Alloaromadendrene, allyl hexanoate, benzaldehyde,(Z)-α-cis-bergamotene, (Z)-α-trans-bergamotene, β-bisabolol,epi-α-bisabolol, β-bisabolene, borneol (camphol), cis-γ-bisabolene,borneol acetate (bornyl acetate), α-cadinene, camphene, camphor,cis-carveol, caryophyllene (β-caryophyllene), α-humulene(α-caryophyllene), γ-cadinene, Δ-3-carene, caryophyllene oxide,1,8-cineole, citral A, citral B, cinnameldehyde, α-copaene (aglaiene),γ-curcumene, β-cymene, β-elemene, γ-elemene, ethyl decdienoate, ethylmaltol, ethyl propionate, ethylvanillin, eucalyptol, α-eudesmol,β-eudesmol, γ-eudesmol, eugenol, cis-β-farnesene ((Z)-β-farnesene),trans-α-farnesene, trans-β-farnesene, trans-γ bisabolene, fenchone,fenchol (norbornanol, β-fenchol), geraniol, α-guaiene, guaiol, methylanthranilate, methyl salicylate, 2-methyl-4-heptanone,3-methyl-4-heptanone, hexyl acetate, ipsdienol, isoamyl acetate,lemenol, limonene, d-limonene (limonene), linolool (linalyl alcohol,β-linolool), α-longipinene, menthol, γ-muurolene, myrcene (β-myrcene),nerolidol, trans-nerolidol, nerol, β-ocimene (cis-ocimene), octylacetate, α-phellandrene, phytol, α-pinene (2-pinene), β-pinene,pulegone, sabinene, cis-sabinene hydrate (cis-thujanol), β-selinene,α-selinene, γ-terpinene, terpinolene (isoterpine), terpineol (aterpineol), terpineol-4-ol, α-terpinene (terpilene), α-thujene(origanene), vanillin, viridiflorene (ledene), α-ylangene. In someembodiments, the concentrates one or more cannabinoid compounds (in thecombinations and w/w percentages described above) in combination withfrom 0.1%, 0.5%, 1%, 2%, 3% to about 5% or 10% of one or more of theterpenoids.

In some embodiments, the concentrate comprise a total cannabinoidfraction of from about 45% to 98% w/w (calculated as a weight percentageof the total weight of the concentrate), most preferably about 65% to95% w/w total cannabinoid compounds and a total terpenoid fraction offrom about 0.1% to 5% w/w total terpenoids (calculated as a weightpercentage of the total weight of the concentrate). In some embodiments,the total cannabinoid fraction contains from about 62% to about 92% w/wor from about 75% to 92% w/w TCHA and THC combined (calculated as aweight percentage of the total weight of the concentrate). In otherembodiments, the total cannabinoid fraction comprises from about 40% to95% w/w or from about 60% to 92% w/w of a combination of CBG, CBC andTHCV (calculated as a weight percentage of the total weight of theconcentrate). As described above, the total cannabinoid fraction mayadditionally comprise at least 1%, 2%, 5%, or 10% w/w of three of thecannabinoid compounds (calculated as a weight percentage of the totalweight of the concentrate). In some embodiments, the concentratecomprises at least 1%, 2%, 5%, or 10% w/w of four of the cannabinoidcompounds (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the concentrate comprises at least1%, 2%, 5%, or 10% w/w of five of the cannabinoid compounds. Likewise,the total terpenoid fraction may additionally comprise at least 0.05%,0.1%, 0.2%, or 0.5% w/w of two of the terpenoids (calculated as a weightpercentage of the total weight of the concentrate). In some embodiments,the total terpenoid fraction may additionally comprise at least 0.05%,0.1%, 0.2%, or 0.5% w/w of three of the terpenoids (calculated as aweight percentage of the total weight of the concentrate). In someembodiments, the total terpenoid fraction may additionally comprise atleast 0.05%, 0.1%, 0.2%, or 0.5% w/w of four of the terpenoids(calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.05%, 0.1%, 0.2%, or 0.5% w/w of five ofthe terpenoids (calculated as a weight percentage of the total weight ofthe concentrate).

In some preferred embodiments, the processes of the present inventionutilize natural or pharmaceutically acceptable oxidizing agents toquickly oxidize a high THC cannabinoid extract to contain high levels ofcannabinol. The oxidation procedure may be conducted at any time duringthe extraction or concentration process steps described above. In someembodiments, a high THC(a) extract is utilized in the process with orwithout an optional decarboxylation step (heating or chemical) toconvert the THC(a) to THC before the oxidation step. In some preferredembodiments, the extract or concentrate is dissolved in a solvent (e.g.,ethanol). Next, an oxidizing agent is added. Preferred oxidizing agentsinclude hydrogen peroxide and ozone, which can be preferably usedwithout heating. Other suitable oxidizing agents include, but are notlimited to halogens, sulfuric acid, peroxydisulfuric acid, permanganatecompounds, nitrous oxide, and the like. In some embodiments, more than10%, 20, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the THC in theextract or concentrate is converted to a CBN-type cannabinoid.

In some embodiments, the converted concentrates comprise a totalcannabinoid fraction of from about 45% to 98% w/w (calculated as aweight percentage of the total weight of the concentrate), mostpreferably about 65% to 95% w/w total CBN-type compounds (e.g., aslisted above) and a total terpenoid fraction of from about 0.1% to 5%w/w total terpenoids (e.g., as listed above; calculated as a weightpercentage of the total weight of the concentrate). In some embodiments,the total cannabinoid fraction contains from about 62% to about 92% w/wor from about 75% to 92% w/w CBN-type compounds (calculated as a weightpercentage of the total weight of the concentrate). As described above,the total cannabinoid fraction may additionally comprise at least 1%,2%, 5%, or 10% w/w of three or more of the cannabinoid compounds(calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the concentrate comprises at least1%, 2%, 5%, or 10% w/w of four or more of the cannabinoid compounds(calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the concentrate comprises at least1%, 2%, 5%, or 10% w/w of five or more of the cannabinoid compounds.Likewise, the total terpenoid fraction may additionally comprise atleast 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of two or more of theterpenoids (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w ofthree or more of the terpenoids (calculated as a weight percentage ofthe total weight of the concentrate). In some embodiments, the totalterpenoid fraction may additionally comprise at least 0.01%, 0.05%,0.1%, 0.2%, or 0.5% w/w of four or more of the terpenoids (calculated asa weight percentage of the total weight of the concentrate). In someembodiments, the total terpenoid fraction may additionally comprise atleast 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w of five or more of theterpenoids (calculated as a weight percentage of the total weight of theconcentrate). In some embodiments, the total terpenoid fraction mayadditionally comprise at least 0.01%, 0.05%, 0.1%, 0.2%, or 0.5% w/w often or more of the terpenoids (calculated as a weight percentage of thetotal weight of the concentrate). It should be noted that in definingthe concentrates in weight percentage terms, the weight percentage ofthe combined components will not exceed 100%. It should be noted that indefining the concentrates in weight percentage terms, the weightpercentage of the combined components will not exceed 100%.

In some embodiments, dry Cannabis extracts or concentrates may betreated with ozone to effect oxidation. Ozone is a beneficial agent forprocesses where water is undesirable in the final product. Extracts orconcentrates can likewise be treated with UV or visible light in thepresence of oxygen. This is a slower process, less predictable, withlower efficiency. However, the advantage of this process is that thereare no added chemicals or reagents and it can also be performed on ‘dry’Cannabis extracts.

The concentrates, extracts and converted extracts of the presentinvention may be formulated in a variety of ways. In some embodiments,the concentrates may be used either for smoking or in a vaporizationsystem. In some embodiments, the mechanically mixed (e.g., whipped)products are particularly suitable for these uses. There are numerousdevices on the market designed to vaporize Cannabis extracts forinhalation. The composition of the mechanically mixed product is suchthat it is easy to handle, visually unique and appealing due to the clayor wax-like consistency and light color. The concentrates alsopreferably are enriched for terpenoids that add the characteristic aromaof Cannabis flowers that is favored by consumers of these types ofextracts.

In some embodiments, the concentrates are utilized as an activeingredient in a thin film delivery device for use as a sublingual orbuccal delivery system. In preferred embodiments, the thin films aredesigned to be quick dissolving to administer a dose of 2 to 200 mg ofthe concentrates per application directly to the blood stream viaadsorption through the buccal or oral mucosa. The thin films arepreferably formed using standard solvent casting or heat extrusiontechniques. The thin films optionally include a solubilizer, includingone or more of the cyclodextrin compounds (including, but not limitedto, β-cyclodextrin, α-cyclodextrin, γ-cyclodextrin, hydroxypropylβ-cyclodextrin, and randomly methylated β-cyclodextrin), one or moretypes of cyclodextrin polymers, liposomes, micelles, dendrimers, etc. Inpreferred embodiments, the increased solubility provided by the compoundincreases the bio-availability of the active ingredients. In preferredembodiments, the excipients used for construction of the film include abase polymer consisting of at least 35% w/v of the final products. Forthe base polymer one or more of the following common quick dissolvingedible polymers is preferably used: hydroxylpropyl methyl cellulose(hypromellose, HPMC, Methocel, Metolose, Benecel), hydroxy propylcellulose (hyprolose, Klucel, Nisso HPC), starch and modified starch(Amido, amylum, PharmGel, Fluftex W, Instant pure-Cote, Melogel,),pullulan (Pullulane, 1,6 α linked maltotriose), pectin (Citrus pectin,Methopectin, pectin, pectinic acid), gelatin (Byco, cryogel, Instagel,Solugel), and carboxy methyl cellulose (Akulell, Blanose, Aquasorb, CMCsodium).

In some embodiments, additional polymers are used to improve theproperties of the thin film. Polymers that alter the disintegrationproperties of the film are used to make the thin film dissolve faster ormore slowly. In some embodiments, mucoadhesive/bioadhesive polymers areoptionally used to promote adhesion of the strip. These include xanthangum, guar gum, locust bean gum, polycarbophil, cellulose derivatives,polyacyrlic acid, polycarbophil, and thiolated polymers. In someembodiments, plasticizers are used to reduce cracking or brittleness ofthe thin film by improving flexibility. Suitable plasticizers includemaltodextrin, sorbitol, mannitol, glycerol, glycerine, propylene glycol,polyethylene glycols, triethyl citrate, tributyl citrate, acetylcitrate, triacetin, dimethyl phthalate, diethyl phthalate, dibutylphthalate, castor oil, etc. In preferred embodiments, plasticizers areincluded from 5% to 30% w/v of the total formulation.

The thin film can preferably be designed for quick dissolution, or cancomprise a polymer backing to slow the rate of dissolution. This allowsfor a more slow release into the target mucosal surface and discouragesoral ingestion of the active ingredients.

The thin film may optionally include additional additives andexcipients, such as taste-masking agents, flavoring agents, sweeteners,saliva stimulators, and hardening and thickening agents. These additivesand excipients will generally be included in an amount of about 1% to15% w/v of the thin film.

In some preferred embodiments, the present invention provides a chewinggum comprising a concentrate as described in detail above. The chewinggum may preferably be used as a health aid, natural treatment formedical symptoms, or for an intended psychoactive effect on the user andwould be beneficial as a slow release oral mucosal or buccal deliveryvehicle. In preferred embodiments, the chewing gum comprises from about0.01 to 35% of a concentrate as described above. The chewing gum maypreferably contain a sweetener (artificial or natural) as well asartificial and/or natural flavors. Optionally, the chewing gum can becoated with a shell consisting of sweetener, flavors, wetting agents,and solubility/bioavailability enhancers. The shell optionally containscannabinoids. In preferred embodiments, the gum contains greater than40% gum base. In some embodiments, the gum includes an optionalsolubilizer, for example, one or more of the cyclodextrin compounds(including, but not limited to, β-cyclodextrin, α-cyclodextrin,γ-cyclodextrin, hydroxypropyl β-cyclodextrin, and randomly methylatedβ-cyclodextrin), one or more types of cyclodextrin polymers, liposomes,micelles, dendrimers, etc. In preferred embodiments, the increasedsolubility provided by the compound increases the bio-availability ofthe active ingredients.

The present invention also encompasses other formulations of theconcentrates. The concentrates may further be formulated with acceptableexcipients and/or carriers for oral consumption. The carrier may be aliquid, gel, gelcap, capsule, powder, solid tablet (coated ornon-coated), tea, or the like. Suitable excipient and/or carriersinclude maltodextrin, calcium carbonate, dicalcium phosphate, tricalciumphosphate, microcrystalline cellulose, dextrose, rice flour, magnesiumstearate, stearic acid, croscarmellose sodium, sodium starch glycolate,crospovidone, sucrose, vegetable gums, lactose, methylcellulose,povidone, carboxymethylcellulose, corn starch, and the like (includingmixtures thereof). Preferred carriers further include calcium carbonate,magnesium stearate, maltodextrin, and mixtures thereof. The variousingredients and the excipient and/or carrier are mixed and formed intothe desired form using conventional techniques. The tablet or capsule ofthe present invention may be coated with an enteric coating thatdissolves at a pH of about 6.0 to 7.0. A suitable enteric coating thatdissolves in the small intestine but not in the stomach is celluloseacetate phthalate. Further details on techniques for formulation for andadministration may be found in the latest edition of Remington'sPharmaceutical Sciences (Maack Publishing Co., Easton, Pa.). Suchformulations may preferably comprise from about 1 to 200 mg of theconcentrate. Where the formulation is an oral delivery vehicle such as acapsule or tablet, the oral delivery vehicle may preferably comprisefrom about 1 to 200 mg of the concentrate, 10 to 200 mg of theconcentrate to 10 to 100 mg of the concentrate. A daily dosage maycomprise 1, 2, 3, 4 or 5 of the oral delivery vehicles.

In other embodiments, the concentrates are provided as a powder orliquid suitable for adding by the consumer to a food or beverage. Forexample, in some embodiments, the concentrate can be administered to anindividual in the form of a powder, for instance to be used by mixinginto a beverage, or by stirring into a semi-solid food such as apudding, topping, sauce, puree, cooked cereal, or salad dressing, forinstance, or by otherwise adding to a food.

The concentrates of the present invention may be combined with one ormore additional bioactive agents, phytonutrients, or nutraceuticalagents to provide a dietary supplement. In some embodiments, the one ormore additional bioactive agents, phytonutrients, or nutraceuticalagents is from a source other than Cannabis. The dietary supplement maycomprise one or more inert ingredients, especially if it is desirable tolimit the number of calories added to the diet by the dietarysupplement. For example, the dietary supplement of the present inventionmay also contain optional ingredients including, for example, herbs,vitamins, minerals, enhancers, colorants, sweeteners, flavorants, inertingredients, and the like. For example, the dietary supplement of thepresent invention may contain one or more of the following: ascorbates(ascorbic acid, mineral ascorbate salts, rose hips, acerola, and thelike), dehydroepiandosterone (DHEA), Fo-Ti or Ho Shu Wu (herb common totraditional Asian treatments), Cat's Claw (ancient herbal ingredient),green tea (polyphenols), inositol, kelp, dulse, bioflavinoids,maltodextrin, nettles, niacin, niacinamide, rosemary, selenium, silica(silicon dioxide, silica gel, horsetail, shavegrass, and the like),spirulina, zinc, and the like. Such optional ingredients may be eithernaturally occurring or concentrated forms. Nutraceutical agents arenatural, bioactive chemical compounds that have health promoting,disease preventing or medicinal properties. Examples of nutraceuticalagents that may be combined with the concentrates of the presentinvention include, but are not limited to, resveratrol, fucoidan, Alliumcepa, Allium sativum, Aloe vera, Angelica Species, Naturally OccurringAntioxidants, Aspergillus oryzae, barley grass, Bromelain, Carnitine,carotenoids and flavonoids, Catechin, Centella asiatica (Gotu kola),Coenzyme Q10, Chinese Prepared Medicines, Coleus forskohlii, Commiphoramukul, Conjugated Linoleic Acids (CLAs), Crataegus oxyacantha(Hawthorne), Curcuma longa (Turmeric), Echinacea Species (PurpleConeflower), Eleutherococcus senticosus (Siberian Ginseng), EphedraSpecies, Dietary Fish Oil, Genistein, Ginkgo biloba, Glycyrrhiza(Licorice), Hypericum perforatum (St. John's Wort), Hydrastis(Goldenseal) and other Berberine-containing plants, Lactobacillus,Lobelia (Indian Tobacco), Melaleuca alternifolia, Menaquinone, Menthapiperita, n-glycolylneuraminic acid (NGNA), Panax Ginseng, PancreaticEnzymes, Piper mythisticum, Procyanidolic Oligomers, Pygeum africanum,Quercetin, Sarsaparilla species, Serenoa repens (Saw palmetto, Sabalserrulata), Silybum marianum (Milk Thistle), Rosemary/Lemon balm,Selenite, Tabebuia avellanedae (LaPacho), Taraxacum officinale,Tanacetum parthenium (Feverfew), Taxol, Uva ursi (Bearberry), Vacciniummyrtillus (Blueberry), Valerian officinalis, Viscum album (Mistletoe),Vitamin A, Beta-Carotene and other carotenoids, and Zingiber officinale(Ginger).

In some embodiments, the dietary supplements further comprise vitaminsand minerals including, but not limited to, calcium phosphate oracetate, tribasic; potassium phosphate, dibasic; magnesium sulfate oroxide; salt (sodium chloride); potassium chloride or acetate; ascorbicacid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calciumpantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxinehydrochloride; thiamin mononitrate; folic acid; biotin; chromiumchloride or picolonate; potassium iodide; sodium selenate; sodiummolybdate; phylloquinone; vitamin D₃; cyanocobalamin; sodium selenite;copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.Suitable dosages for vitamins and minerals may be obtained, for example,by consulting the U.S. RDA guideline

In other embodiments, the present invention provides nutritionalsupplements (e.g., energy bars or meal replacement bars or beverages)comprising a concentrate as described above. The nutritional supplementmay serve as meal or snack replacement and generally provide nutrientcalories. Preferably, the nutritional supplements provide carbohydrates,proteins, and fats in balanced amounts. The nutritional supplement canfurther comprise carbohydrate, simple, medium chain length, orpolysaccharides, or a combination thereof. A simple sugar can be chosenfor desirable organoleptic properties. Uncooked cornstarch is oneexample of a complex carbohydrate. If it is desired that it shouldmaintain its high molecular weight structure, it should be included onlyin food formulations or portions thereof which are not cooked or heatprocessed since the heat will break down the complex carbohydrate intosimple carbohydrates, wherein simple carbohydrates are mono- ordisaccharides. The nutritional supplement contains, in one embodiment,combinations of sources of carbohydrate of three levels of chain length(simple, medium and complex; e.g., sucrose, maltodextrins, and uncookedcornstarch).

Sources of protein to be incorporated into the nutritional supplement ofthe invention can be any suitable protein utilized in nutritionalformulations and can include whey protein, whey protein concentrate,whey powder, egg, soy flour, soy milk soy protein, soy protein isolate,caseinate (e.g., sodium caseinate, sodium calcium caseinate, calciumcaseinate, potassium caseinate), animal and vegetable protein andmixtures thereof. When choosing a protein source, the biological valueof the protein should be considered first, with the highest biologicalvalues being found in caseinate, whey, lactalbumin, egg albumin andwhole egg proteins. In a preferred embodiment, the protein is acombination of whey protein concentrate and calcium caseinate. Theseproteins have high biological value; that is, they have a highproportion of the essential amino acids. See Modern Nutrition in Healthand Disease, eighth edition, Lea & Febiger, publishers, 1986, especiallyVolume 1, pages 30-32.

The nutritional supplement can also contain other ingredients, such asone or a combination of other vitamins, minerals, antioxidants, fiberand other dietary supplements (e.g., protein, amino acids, choline,lecithin, omega-3 fatty acids). Selection of one or several of theseingredients is a matter of formulation, design, consumer preference andend-user. The amounts of these ingredients added to the dietarysupplements of this invention are readily known to the skilled artisan.Guidance to such amounts can be provided by the U.S. RDA doses forchildren and adults. Further vitamins and minerals that can be addedinclude, but are not limited to, calcium phosphate or acetate, tribasic;potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodiumchloride); potassium chloride or acetate; ascorbic acid; ferricorthophosphate; niacinamide; zinc sulfate or oxide; calciumpantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxinehydrochloride; thiamin mononitrate; folic acid; biotin; chromiumchloride or picolonate; potassium iodide; sodium selenate; sodiummolybdate; phylloquinone; vitamin D₃; cyanocobalamin; sodium selenite;copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.

Flavors, coloring agents, spices, nuts and the like can be incorporatedinto the product. Flavorings can be in the form of flavored extracts,volatile oils, chocolate flavorings, peanut butter flavoring, cookiecrumbs, crisp rice, vanilla or any commercially available flavoring.Examples of useful flavoring include, but are not limited to, pure aniseextract, imitation banana extract, imitation cherry extract, chocolateextract, pure lemon extract, pure orange extract, pure peppermintextract, imitation pineapple extract, imitation rum extract, imitationstrawberry extract, or pure vanilla extract; or volatile oils, such asbalm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil,cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolateflavoring, vanilla cookie crumb, butterscotch or toffee. In oneembodiment, the dietary supplement contains cocoa or chocolate.

Emulsifiers may be added for stability of the final product. Examples ofsuitable emulsifiers include, but are not limited to, lecithin (e.g.,from egg or soy), and/or mono- and di-glycerides. Other emulsifiers arereadily apparent to the skilled artisan and selection of suitableemulsifier(s) will depend, in part, upon the formulation and finalproduct.

Preservatives may also be added to the nutritional supplement to extendproduct shelf life. Preferably, preservatives such as potassium sorbate,sodium sorbate, potassium benzoate, sodium benzoate or calcium disodiumEDTA are used.

In addition to the carbohydrates described above, the nutritionalsupplement can contain natural or artificial (preferably low calorie)sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame,acesulfame K, and/or sorbitol. Such artificial sweeteners can bedesirable if the nutritional supplement is intended to be consumed by anoverweight or obese individual, or an individual with type II diabeteswho is prone to hyperglycemia.

The nutritional supplement can be provided in a variety of forms, and bya variety of production methods. In a preferred embodiment, tomanufacture a food bar, the liquid ingredients are cooked; the dryingredients are added with the liquid ingredients in a mixer and mixeduntil the dough phase is reached; the dough is put into an extruder, andextruded; the extruded dough is cut into appropriate lengths; and theproduct is cooled. The bars may contain other nutrients and fillers toenhance taste, in addition to the ingredients specifically listedherein.

In still further embodiments, the present invention provides functionalfoods, including food products, prepared food products, or foodstuffscomprising a concentrate as described above. For example, in someembodiments, beverages and solid or semi-solid foods comprising sulfatedpolysaccharides (e.g., fucoidan) are provided. These forms can include,but are not limited to, beverages (e.g., soft drinks, milk and otherdairy drinks, and diet drinks), baked goods, puddings, dairy products,confections, snack foods, or frozen confections or novelties (e.g., icecream, milk shakes), prepared frozen meals, candy, snack products (e.g.,chips), soups, spreads, sauces, salad dressings, prepared meat products,cheese, yogurt and any other fat or oil containing foods, and foodingredients (e.g., wheat flour).

In preferred embodiments, an effective amount of the concentrate tocause the desired physiological response is provided to a subject,preferably in a once a day or twice a day dosage. In preferredembodiments, an effective amount of the concentrate is from 1-5000 mg ofthe concentrate, and most preferably from 100-2000 mg of the concentrateor 200 to 1000 mg of the concentrate daily. In some embodiments, theeffective amount is the amount necessary to reduce inflammation, reducepain, reduce nausea, enhance mood, produce a calm feeling, inducedrowsiness or sleep, reduce anxiety, support joint health, supportmental health, support anti-inflammatory response by the body, supportbrain function, support feelings of wellbeing, support healthy skin andreduce blemishes.

EXAMPLES Example 1 Preparation of Trichome Concentrate

Method 1A

Materials and Methods

Equipment:

A mechanical tumbler with a cylindrical barrel made of a steel meshcontaining 170 micron pores. The barrel lies horizontally and is beltdriven by an electric motor. The barrel portion is placed inside of abox with a collection pan at the bottom.

Methods:

200 g of dried Cannabis plant material from clones of the same varietyof a drug strain of Cannabis sativa consisting of small flowers andtrichome laden leaves was placed inside the tumbler and the motor turnedon for differing lengths of time. The duration of extraction included 5minutes, 15 minutes, one hour, and 6 hours. After the extraction, thetrichome heads were collected as a dry powder in the bottom pan of thecollection box.

This method can be extended to any process which agitates the plantmaterial over a mesh screen to allow the trichome heads to fall throughwhile catching the majority of plant material. Also, an optional step tofreeze the plant material at −20 C to −70 C to cause the trichomes to bebrittle before being placed in the tumbler was found to increase yieldand improve quality of the extract. Dry ice was found to be a verysuitable method for freezing the plant material because it preventedmoisture buildup on the plant material. Pieces of dry ice can also beplaced inside of the extraction tumbler to keep the plant material coldthroughout the process and assist in agitation of the plant materialwere also found to be useful.

Results:

The longer the duration of the extraction, the greater the yield oftrichome heads. Yields per 200 g were from 11 g (5.5%) for the 5 minuteextraction, 18 g (9%) for the 15 minute extraction, 22 g (11%) for the 1hour extraction, to 29 g (14.5%) for the 6 hour extraction.

The concentration of cannabinoids as measured using HPLC/DAD decreasedwith increasing extraction times and yields. Total cannabinoids(THC+THCA+CBD+CBDA+CBN) concentrations ranged from 49% for the 5 minuteextraction, 40% for the 15 minute extraction, 34% for the 1 hourextraction, and 26% for the 6 hour extraction.

The color of the collected heads ranged from light tan for the 5 minuteextract to a darker, slightly greenish, brown for the 6 hour extraction.

Method 2A:

Materials:

A large nylon cylinder was constructed of nylon mesh with a 180 micronpore diameter. The cylinder was entirely enclosed and a zipper was sewnin to allow access to the inside. A nylon bag large enough to fit themesh cylinder inside of it was also constructed with a zipper to allowfor access to the inside. The nylon used to construct this bag allowedwater to penetrate but was woven tight enough to not allow any plantmaterial or trichome heads to pass through.

Equipment:

A large drum driven by a belt was mounted inside of a watertightcontainer. The drum had several paddles mounted to the inside of thecylinder to provide for agitation of the contents. The apparatus wasconstructed to allow for the drum to be rotated through the top of thecontainer while it was filled with water.

Method:

400 g of plant material was placed inside the mesh cylinder and it waszipped shut. The cylinder was zipped inside the bag and the bag wasplaced in the drum. The drum apparatus was filled ¾ of the way with icewater. The drum was rotated for 15 minutes, 30 minutes, and 1 hour. Thebag was removed from the drum and allowed to drain of water. The innermesh bag was removed from the outer nylon bag. Inside the nylon bag, amedium light brown to dark, greenish brown, sediment had collected. Thesediment was collected on a glass plate and excess water was pressed outusing a 5 micron mesh nylon screen. The pressed trichome heads wereplaced on a glass plate and vacuum desiccated for 24 hours.

Results:

Trends for this process were similar to the dry method, longerextraction times correlated to higher yields of extract. The yield(after drying) for the 15 minute extraction was 52 g (12%), for the 30minute extraction it was 72 g (18%), and for the 1 hour extraction itwas 89 g (22.3%).

The concentration of cannabinoids as measured using HPLC/DAD decreasedwith increasing extraction times and yields. Total cannabinoids(THC+THCA+CBD+CBDA+CBN) concentrations ranged from 58% for the 15 minuteextraction, 52% for the 30 minute extraction, and 47% for the 1 hourextraction.

Example 2 Extraction from Trichome Concentrate

Method 1B

Gas Extraction

Materials and Equipment:

A pressurized system was constructed with a solvent reservoir mounted ontop of the column and separated by a operator controlled valve. Thecolumn consisted of a stainless steel cylinder with a valve pre-columnleading to the reservoir and filter followed by another operatorcontrolled valve post-column leading to a recovery chamber. The recoverychamber was outfitted with a heating mantle and an outlet valve to allowthe solvent to be released back into the reservoir. All fitting andvalves were airtight and explosion-proof.

Additional materials included tanks of propane, isobutane, and n-butane.All solvents were ultra-high purity grade and purchased from a chemicalsupplier.

200 grams of each of the crude extracts produced according to themethods in the previous description were used as well as 50 grams ofplant material (trichome laden flower leaves and small flowers).Material A was produced by tumbling freshly dried plant material in thecylinder from Method 1, for 30 minutes. It was a light brown color andtested 46% total active cannabinoids by HPLC/DAD. Material B wasproduced by extracting freshly dried plant material in the ice waterextraction equipment from Method 2 for 30 minutes. It was a medium brownin color and tested 59% total active cannabinoids. The crude extractswere made from the same plant material that was used for the experiment.All of the plant material (Material C) consisted of trichome dense smallleaves and small Cannabis flowers and it originated from the same strainof drug-type Cannabis sativa. The homogenized plant material tested 14%total active cannabinoids.

Methods:

Each of the samples was placed in the column. For the fixed size of thecolumn, 200 g of the crude extract occupied approximately the samevolume as 50 g of the plant material. Each extraction was carried out bypassing 400 g of a propane, iso-butane, and n-butane mixture through thecolumn packed with plant material or crude extract. The system waspressurized to ensure the gases were in kept in a liquid state whilepassing through the samples. The eluate was mostly stripped of solventusing the mechanism designed into the equipment. The remaining eluatewas collected on glass petri dishes and placed in a vacuum desiccator.

Data:

The dried extracts were amorphous solids, slightly sticky to touch,ranging from a translucent light yellow orange color for the extractmade from Material A, to a translucent light amber color for Material B,to a darker translucent amber color for material C. Material A yielded98.2 g of final extract with 89.6% active cannabinoids. Material Byielded 122.4 g of final extract with 87.4% active cannabinoids.Material C yielded 5.1 g of final extract that tested 79.0% activecannabinoids.

Method 2B

Liquid Extraction

Materials and Equipment:

A vacuum distiller, n-Pentane, medium porosity sintered glass Buchnerfunnel with filter flask equipment. Various laboratory glassware wasused. Three samples were used for this extraction 100 grams of each ofthe crude extracts produced according to the methods in the previousdescription were used as well as 100 grams of plant material (trichomeladen flower leaves and small flowers). Material A was produced bytumbling freshly dried plant material in the cylinder from Method 1, for30 minutes. It was a light brown color and tested 46% total activecannabinoids by HPLC/DAD. Material B was produced by extracting freshlydried plant material in the ice water extraction equipment from Method 2for 30 minutes. It was a medium brown in color and tested 59% totalactive cannabinoids. The crude extracts were made from the same plantmaterial that was used for the experiment. All of the plant material(Material C) consisted of trichome dense small leaves and small Cannabisflowers and it originated from the same strain of drug-type Cannabissativa. The homogenized plant material tested 14% total activecannabinoids.

Method:

The samples were each placed in 2 L of n-Pentane and lightly stirred for30 seconds. Much less solvent (˜200 ml) would have been needed for thepre-extracted samples, but 2 L was used for each sample in the interestof uniformity. 2 L was the minimum solvent needed to ensure all of theplant material was submerged in solvent. This demonstrates the inherentadvantages of a two-step extraction with regard to minimizing solventuse and volumes necessary to work with. The samples were stirred in thesolvent for a short period of time to avoid dissolving unwanted plantmaterials like chlorophyll.

The plant material was filtered out by pouring the solution through theBuchner funnel. The eluate was then stripped of n-Pentane using a rotaryevaporator.

Data:

The dried extracts were amorphous solids at STP slightly sticky totouch. With a slight warming, they become much more pliable and slightlyrunny. The extract produced with material A was much more translucentand lighter amber in color, the extract produced with material B wasslightly darker but still translucent, the extract produced withmaterial C was opaque and almost black. When held to the light, it had agreen hue to it due to the increased chlorophyll content of thisextract.

Material A yielded 50.2 g of final extract with 88.9% activecannabinoids. Material B yielded 63.0 g of final extract with 84.9%active cannabinoids. Material C yielded 9.2 g of final extract thattested 76.3% active cannabinoids.

Example 3 Processing of Extracts to Form a Waxy Base

Materials:

Concentrated Cannabis extract eluate created from both Method 1A andMethod 1B were utilized. Several whisk attachments were constructed.Some acceptable designs included magnetic stir bars, horizontal wiresradiating from a central point attached to the shaft, an aerated design,an auger type configuration, an auger with a flat blade at the bottom,etc. The most successful design consisted of 6 wire “fish hooks”radiating from the central hub attached to the shaft.

Methods:

The concentrated eluate is continuously stirred by the whisk. Thisoccurred in a fume hood with vacuum desiccation due to the volatilenature of the solvent system. The eluate was placed in a Pyrex tray andthe tray was maintained at 35 C in a water batch. The eluate wascontinuously whipped or whisked until dry. The whipped final product wasa waxy or clay like consistency and had a white to yellow color. Theproduct is opaque. The final product is not tacky to the touch and ismuch easier to handle than the unwhipped extracts. This waxy productbase can optionally have additives mixed mechanically into the waxy baseat this point.

Example 4 Oxidation of THC to CBN

Experiments using ozone, hydrogen peroxide, and UV/visible lightexposure in the presence of oxygen have been able to produce significantamounts of cannabinol from THC or THCa in plant material (H2O2, light)and extracts (O3, H2O2, and light).

Materials and Equipment:

Absolute ethanol, 30% concentrated hydrogen peroxide, several differentpieces of common laboratory glassware and tools, temperature probecontrolled magnetically stirred hot plates, common laboratory grade UVlight used for reading TLC stains, analytical instruments for analysis(including balances, HPLC-DAD, and assorted volumetric measuringinstruments) and Cannabis extract produced using the above methods. TheCannabis extract was decarboxylated using heat and measured forcannabinoid content. The extract measured 70.1% THC, 0.2% THCA, 0.2%CBN, 0.7% CBD, and 0.4% CBDA w/w. Analysis were performed using HPLCwith a DAD detector, with an isocratic gradient of acetonitrile andwater with formic acid, on a reverse phase C18 hplc column. Allstandards were purchased from Restek corporation.

Procedures:

200 ml of an ˜50 mg/ml THC in ethanol solution was prepared bydissolving 14.27 g of the extract in 200 ml of absolute ethanol. 50 mlof the solution was measured and poured into two large, petri disheswhich were labeled A and B. 50 ml of solution was measured and pouredinto a beaker and labeled C. The final 50 ml of solution was placed in afourth beaker and labeled D. A and B were placed in petri dishes tomaximize exposure to a top light source. A, B, C, and D were equippedwith magnetic stir bars and placed on a stirring hotplate with thesolution temperatures set to 40 C. A was placed in direct full spectrumsunlight for 12 hours at 40 C with stirring. B was placed under UV lightfor 12 hours at 40 C with stirring. To C was added 5 ml of the 30%hydrogen peroxide and stirred for 12 hours at 40 C in a low lightenvironment. D was placed on a hot plate at 40 C with stirring andplaced in a low light environment.

Results:

Each sample other than D showed a marked increase in CBN levels.Baseline CBN levels for the stock solution were 0.1 mg/ml. Sample Ameasured 4.6 mg/ml of CBN, Sample B measured 3.5 mg/ml of CBN, Sample Cmeasured 18.3 mg/ml of CBN, and Sample D measured 0.2 mg/ml of CBN.

The invention claimed is:
 1. A tablet or capsule consisting essentiallyof at least 1% w/w each in the total tablet or total capsule of at leasttwo cannabinoids selected from the group consisting of Cannabigerolicacid A (Z)-CBGA-C₅ A, Cannabichromenic acid A CBCA-C₅ A, and CannabinolCBN-C₅ and at least 0.1% w/w each in the total tablet or total capsuleof at least one terpenoid selected from the group consisting ofAlloaromadendrene, allyl hexanoate, benzaldehyde, (Z)-a-cis-bergamotene,(Z)-a-trans-bergamotene, beta-bisabolol, epi-alpha-bisabolol,beta-bisabolene, borneol, c-gamma-bisabolene, borneol acetate,alpha-cadinene, camphene, camphor, cis-carveol, caryophyllene,alpha-humulene, gamma-cadinene, delta-3-carene, caryophyllene oxide,1,8-cineole, citral A, citral B, cinnameldehyde, alpha-copaene,gamma-curcumene, beta-cymene, beta-elemene, gamma-elemene, ethyldecdienoate, ethyl maltol, ethyl propionate, ethylvanillin, eucalyptol,alpha-eudesmol, beta-eudesmol, gamma-eudesmol, eugenol,cis-beta-famesene, trans-gamma bisabolene, fenchone, fenchol, geraniol,alpha-guaiene, guaiol, methyl anthranilate, methyl salicylate,2-methyl-4-heptanone, 3-methyl-4-heptanone, hexyl acetate, ipsdienol,isoamyl acetate, lemenol, limonene, d-limonene, linolool,alpha-longipinene, menthol, gamma-muurolene, myrcene, nerolidol,trans-nerolidol, nerol, beta-ocimene, octyl acetate, alpha-phellandrene,phytol, alpha-pinene, beta-pinene, pulegone, sabinene, cis-sabinenehydrate, beta-selinene, alpha-selinene, gamma-terpinene, terpinolene,terpineol, terpineol-4-ol, alpha-terpinene, alpha-thujene, vanillin,viridiflorene, and alpha-ylange.
 2. The tablet or capsule of claim 1,wherein said tablet or capsule consists essentially of at least 1% w/weach in the total tablet or total capsule of said Cannabigerolic acid A(Z)-CBGA-C₅ A, Cannabichromenic acid A CBCA-C₅ A, and Cannabinol CBN-C₅.3. The tablet or capsule of claim 1, wherein said tablet or capsuleconsists essentially of at least 0.1% each in the total tablet or totalcapsule of two of said terpenoids.
 4. The tablet or capsule of claim 1,wherein said tablet or capsule consists essentially of at least 0.1%each in the total tablet or total capsule of three of said terpenoids.5. The tablet or capsule of claim 1, wherein said tablet or capsule issubstantially free of tetrahydrocannabinol.
 6. The tablet or capsule ofclaim 1, wherein said tablet or capsule consists essentially of at least2% w/w each in the total tablet or total capsule of at least twocannabinoids selected from the group consisting of Cannabigerolic acid A(Z)-CBGA-C₅ A, Cannabichromenic acid A CBCA-C₅ A, and Cannabinol CBN-C₅.7. The tablet or capsule of claim 1, wherein said tablet or capsuleconsists essentially of at least 5% w/w each in the total tablet ortotal capsule of at least two cannabinoids selected from the groupconsisting of Cannabigerolic acid A (Z)-CBGA-C₅ A, Cannabichromenic acidA CBCA-C₅ A, and Cannabinol CBN-C₅.
 8. The tablet or capsule of claim 1,wherein said tablet or capsule consists essentially of at least 10% w/weach in the total tablet or total capsule of at least two cannabinoidsselected from the group consisting of Cannabigerolic acid A (Z)-CBGA-C₅A, Cannabichromenic acid A CBCA-C₅ A, and Cannabinol CBN-C₅.